The 19th Conference on Trans-Pyrenean Investigations in Obesity and Diabetes
held at Residencia Universitaria de Jaca, Aragon, Spain
on 17-18th October 2022
has its research laureates of CTPIOD awards
For the 2022 CTPIOD Research Award of CLINIC RESEARCH, the winner is Léopold DEVINEAUX from TOULOUSE
For the 2022 CTPIOD Research Award of BASIC RESEARCH, the winner is Ester DIEZ-SAINZ from PAMPLONA
The pictures of the laureates are below together with the organizers of the meeting and members of the evaluation committee
from left to right: Fermin MILAGRO (UNAV), Christian CARPENE (I2MC), Mathieu DESPEAUX (Clinique de BONDIGOUX), SILVIA LORENTE (UNIZAR)
All classes of congratulations for the laureates and all the participants
Below are the abstracts of the oral presentations, presented on last october by alphabetical order of the applicants.
Most of these work will be published next year as research articles in a future Special Issue CTPIOD 2022 of the Journal of Physiology and Biochemistry (Springer Eds, IF 5.1), together with a collaborative review of multiple aspects of polyphenol interests in combatting diabates and obesity. Meanwhile, the previous SI CTPIOD 2021 is in press, reday to be published soon, and some articles are already indexed in PubMed and available on the net.
held at Residencia Universitaria de Jaca, Aragon, Spain
on 17-18th October 2022
has its research laureates of CTPIOD awards
For the 2022 CTPIOD Research Award of CLINIC RESEARCH, the winner is Léopold DEVINEAUX from TOULOUSE
For the 2022 CTPIOD Research Award of BASIC RESEARCH, the winner is Ester DIEZ-SAINZ from PAMPLONA
The pictures of the laureates are below together with the organizers of the meeting and members of the evaluation committee
from left to right: Fermin MILAGRO (UNAV), Christian CARPENE (I2MC), Mathieu DESPEAUX (Clinique de BONDIGOUX), SILVIA LORENTE (UNIZAR)
All classes of congratulations for the laureates and all the participants
Below are the abstracts of the oral presentations, presented on last october by alphabetical order of the applicants.
Most of these work will be published next year as research articles in a future Special Issue CTPIOD 2022 of the Journal of Physiology and Biochemistry (Springer Eds, IF 5.1), together with a collaborative review of multiple aspects of polyphenol interests in combatting diabates and obesity. Meanwhile, the previous SI CTPIOD 2021 is in press, reday to be published soon, and some articles are already indexed in PubMed and available on the net.
Comparative effects of a probiotic and a parabiotic administration in the prevention of diet-induced insulin resistance in rats
Laura Arellano-García 1, Iñaki Milton-Laskibar 1,2,3*, J. Alfredo Martínez 2,4 and María P. Portillo 1,2,3
1 Nutrition and Obesity Group; [email protected]
2 CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN); [email protected]; [email protected]; [email protected]
3 BIOARABA Institute of Health
4 Precision Nutrition and Cardiometabolic Health, IMDEA-Food Institute (Madrid Institute for Advanced Studies)
Obesity prevalence has been on the rise for the last decades, reaching pandemic dimensions, and the prevalence of obesity-related disorders, such as type II diabetes (T2D), has also increased concomitantly [1,2]. Among the main factors contributing to obesity and T2DM, unhealthy dietary patterns and a sedentary lifestyle stand out [3]. These factors also contribute to gut microbiota dysbiosis, which has been described in both, obesity and T2DM [4,5].
The aim of this research project is to analyze the efficacy of the administration of a parabiotic (heat- inactivated L. rhamnosus GG) in comparison to the administration of the same viable probiotic in the prevention of diet induced insulin resistance.
To do so 36 male Wistar rats were randomly distributed in 4 groups (n=9) and fed either a standard diet (C group) or a high-fat high-fructose diet alone (HFHF group), combined with a probiotic (L. rhamnosus GG, 109 CFU/day, PRO group) or with a parabiotic (heat-inactivated probiotic, same dose, PARA group).
The increased serum glucose and insulin levels found in the HFHF group were significantly reverted in the PRO and PARA groups. Adiponectin and leptin levels, as well as the adiponectin/leptin ratio were significantly higher in the PRO group compared to the HFHF group. Significant reductions in the TG/glucose and HOMA-IR indexes were found in the PRO and PARA groups compared to the HFHF group. As for insulin signaling cascade, both the PRO and the PARA groups showed a tendency towards higher insulin receptor phosphorylation (p < 0.1) compared to the HFHF group. The parabiotic administration tended to increase Akt phosphorylation (p < 0.1) compared to the HFHF group. The PRO group showed significantly higher phosphorylation of AS160 compared to the HFHF animals, while a tendency towards a higher phosphorylation rate was observed in the PARA animals (p = 0.063). No changes in GLUT4 protein expression were found in the treated groups.
According to the obtained results, the administration of a parabiotic or its probiotic of origin similarly prevent diet induced insulin resistance in rats, despite the involved mechanisms of action seem not to be exactly the same.
This project is supported by CIBERobn under Grant CB12/03/30007 and the Community of Madrid under Grant Y2020/BIO-6600.
References:
- Chooi, Y., Ding, C., & Magkos, F. (2019). The epidemiology of obesity. Metabolism, 92, 6-10. doi: 10.1016/j.metabol.2018.09.005
- Colosia, A. D., Palencia, R., & Khan, S. (2013). Prevalence of hypertension and obesity in patients with type 2 diabetes mellitus in observational studies: a systematic literature review. Diabetes, metabolic syndrome and obesity : targets and therapy, 6, 327–338. https://doi.org/10.2147/DMSO.S51325
- Statovci D, Aguilera M, MacSharry J, Melgar S. The Impact of Western Diet and Nutrients on the Microbiota and Immune Response at Mucosal Interfaces. Front Immunol. 2017 Jul 28;8:838. doi: 10.3389/fimmu.2017.00838.
- Cuevillas B, Milagro FI, Tur JA, Gil-Campos M, de Miguel-Etayo P, Martínez JA, Navas-Carretero S. Fecal microbiota relationships with childhood obesity: A scoping comprehensive review. Obes Rev 2022, 23 Suppl 1, e13394.
- Li WZ, Stirling K, Yang JJ, Zhang L. Gut microbiota and diabetes: From correlation to causality and mechanism. World Journal of Diabetes 2020, 11, 293-308.
Adaptation of adipose tissue microvascular endothelium adaptive response to energy transition state:
contribution of DLL4
Alex Aupetit 1, Pauline Decaunes 1, Chloé Belles 1, Elodie Riant 2, Jean Galitzky 1, Benoit Chaput 3, Katell Vié 4, Jean-François Arnal 2, Anne Bouloumié 1, Anaïs Briot 1
1 Institute of Metabolic and Cardiovascular Diseases, INSERM, UMR1048, Team DYNAMIX, I2MC, CHU Rangueil, France.
2 Institute of Metabolic and Cardiovascular Diseases, INSERM, UMR1048, Team ESTER, I2MC, CHU Rangueil, France.
3 Department of Plastic and Reconstructive Surgery, Toulouse University Hospital, Toulouse, France.
4 Laboratoires Clarins, Pontoise, France. Correspondence: Anaïs Briot - [email protected]
Metabolic flexibility is defined as the ability to adapt oxidative metabolism (fatty acid versus carbohydrate) according to energy transition state. Deterioration of the homeodynamic process is associated with cardio-metabolic disorders but the underlying mechanisms remain unclear. Vascular endothelial cells (EC) from the adipose tissue (AT) plays a central role in metabolic flexibility through the bidirectional transport of fatty acids (FA). In fed condition, FA are channeled from blood towards adipocytes while during fasting, they are mobilized from adipocytes to the blood stream. However how the endothelial cells sense changes in energy transition state and adapt FA transport according to fat depot remain to be defined.
To gain insight, we studied AT-EC immuno-selected from paired human abdominal and femoral subcutaneous AT. In parallel, we assessed AT-EC dynamic adaptation to energy transition in C57Bl/6 mice submitted to fed/fasted/refed challenges.
Transcriptional large scale analysis of human AT-EC revealed that the endothelium transcriptome carries a fat depot-specific signature associated with FA handling and Notch signaling. In vitro approaches in human and ex vivo study of mouse AT-EC highlighted a functional link between metabolic status and the Notch ligand DLL4. DLL4, the level of which is modulated by fasting in vivo and fasting-activated pathways in vitro, regulates the uptake of long-chain FA by AT-EC. Importantly, this energy state-dependent Dll4 modulation in AT-EC is impaired under obesogenic condition.
Our study provides evidences that the endothelium actively adapts to energy transition state. It identifies DLL4 as a metabolic hub relaying clues to the endothelium to handle lipid fluxes. The associated mechanisms likely contribute to define metabolic flexibility. However, their alteration with obesity may favor metabolic inflexibility and the development of cardio-metabolic disorders.
This work is supported by funds from the French National Institute for Health and Medical Research (Inserm), Université Paul Sabatier Toulouse and Région Occitanie, Association Française d’étude et de Recherche sur l’obésité (AFERO) and Société Francophone du diabète (SFD).
Comparison of the effect of Opuntia ficus-indica and Opuntia stricta var. Dillenii extracts in the prevention of triglyceride accumulation in mouse AML-12 hepatocytes
Irene Besné-Eseverri 1*, Jenifer Trepiana 1, 2, 3, Pilar Cano 4, María P. Portillo 1, 2, 3
1 Nutrition and Obesity Group, Department of Nutrition and Food Sciences, Faculty of Pharmacy, University of the Basque Country (UPV/EHU) and Lucio Lascaray Research Institute, Vitoria-Gasteiz, Spain, 2 BIOARABA Health Research Institute, Vitoria-Gasteiz, Spain, 3 CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Vitoria-Gasteiz, Spain; 4 Laboratory of Phytochemistry and Plant Food Functionality, Biotechnology and Food Microbiology Department, Institute of Food Science Research (CIAL) (CSIC-UAM), Madrid, Spain.
*Email for correspondence: [email protected]
Steatosis is characterized by excessive hepatic lipid accumulation as triglycerides. Opuntia Spp. from the Cactacea family shows in its composition flavonoids, phenolic acids and betalains that could help in the prevention of steatosis. The most investigated species is Opuntia ficus-indica (OFI), which contains a great variety of glycosylate isorhamnetins and indicaxanthin. Opuntia stricta var. Dillenii (OD) grows in arid climates, such as Canary Islands, Murcia and Almeria and is of great interest because it has specific compounds, such as neobetanin and phyllocactin. This study aims to compare the reduction of triglyceride accumulation induced in hepatocytes incubated with OFI or OD extracts. An in vitro model mimicking the hepatocyte situation in fatty liver was developed by incubating mouse AML-12 hepatocytes with palmitic acid (0.3 M). For the treatment, cells were incubated with peel and pulp extracts of different varieties of OFI, Pelota, Colorada and Sanguinos, at 25, 50, 100 or 200 µg/mg or with OD extracts from fresh fruits (peel, pulp or whole fruit) or the wastes of food industry (bagasse) at 10, 25, 50 or 100 µg/mg. Triglycerides and cell viability were assessed by using a commercial kit and crystal violet assay, respectively. All OD extracts significantly reduced triglyceride accumulation at some doses, while Pelota and Colorada peel extracts did not show this effect. The most effective extract in the case of OFI was Sanguinos pulp at 100 µg/mg (23.29 % triglyceride reduction). In the case of OD, it was the peel at 10 µg/mg (36.9 % reduction) the most effective extract at the lowest dose. None of the extracts affected cell viability. In view of the results, OD is a more interesting variety than OFI in the prevention of steatosis.
This project is supported by the Spanish Ministery of Science and Inovation, project number PID2020-118300RB-C22 and a FPI predoctoral grant.
References:
1. Gómez-López, I.; Lobo-Rodrigo, G.; Portillo, M.P.; Cano, M.P. Characterization, Stability, and Bioaccessibility of Betalain and Phenolic Compounds from Opuntia stricta var. Dillenii Fruits and Products of Their Industrialization. Foods 2021, 10, 1593. doi: /10.3390/foods10071593.
HDL-borne triglycerides are associated with insulin resistance in patients with Hepatitis C undergoing direct-acting antiviral treatment
Diego Casas-Deza 1,2*, Maria Pilar García-Sobreviela 2,3, Raquel del Moral-Bergos 2,3, Marta Lopez-Yus 2,3, Vanesa Bernal-Monterde 1,2, Jose M. Arbones-Mainar 2,3,4
1 Gastroenterology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain; 2 Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain; 3 Translational Research Unit, Miguel Servet University Hospital, Instituto Aragonés de Ciencias de la Salud (IACS), 50009 Zaragoza, Spain; 4 Centro de Investigación Biomédica en Red Fisiopatología Obesidad y Nutrición (CIBERObn), Madrid, Spain
Hepatitis C virus (HCV) interferes with carbohydrate and lipid metabolism causing, among others, liver steatosis, insulin resistance (IR), and cardiovascular disease. We recently showed a reduced insulin resistance after HCV eradication, although paradoxically associated with increased total and LDL-cholesterol (1). We hypothesize that other changes in the lipoprotein content might be driven this counterintuitive association. Therefore, our objective is to evaluate the DAA-associated changes in lipoparticles and its association with insulin resistance.
Prospective study with one-year follow-up. All naive patients treated with DAAs in the Liver Clinic of the Miguel Servet University Hospital were included. Those co-infected with HBV or HIV were excluded. Insulin resistance was analyzed using the HOMA index. Lipoproteins were studied by Diffusion Ordered Nuclear Magnetic Resonance Spectroscopy (DOSY-NMR).
During follow-up there was a concomitant increase in LDL cholesterol and an improvement in HOMA. However, we observed a sustained decrease in HDL triglyceride content, but not in LDL- or VLDL-borne triglycerides. Consistent with this finding, a decrease in HDL particle size was also observed. This reduced content of triglycerides transported by HDL may explain, at least partially, the improvement in insulin sensitivity after DAA treatment.
This project was supported by a Gilead Fellowship. D.C.-D. is partially supported by a Rio-Hortega fellowship from Instituto de Salud Carlos III.
References:
1 - Casas-Deza, D.; Martínez-Sapiña, A.; Espina, S.; Garcia-Rodriguez, B.; Fernandez-Bonilla, E.M.; Sanz-Paris, A.; Gonzalez-Irazabal, Y.; Bernal-Monterde, V.; Arbones-Mainar, J.M. Evaluation of Cardiovascular Risk Factors after Hepatitis C Virus Eradication with Direct-Acting Antivirals in a Cohort of Treatment-Naïve Patients without History of Cardiovascular Disease. J. Clin. Med. 2022, 11, 4049. https:// doi.org/10.3390/jcm11144049
Fibro-Caps, a 3D model mimicking alterations of a fibrotic microenvironment on the metabolism of human mature adipocytes
Léopold Devineaux, Marion Bourdens, Danièle Lacasa and Mayoura Kéophiphath
DIVA Expertise, 1 Place Pierre Potier, 31100 Toulouse, France
During cellulite, obesity or aging, immune cells can accumulate in adipose tissue (AT) contributing to the development of a local and low grade inflammation. Chronicization of this inflammatory state can lead to an intense remodelling of extracellular matrix that can be qualified as fibrosis. Clinically, this fibrotic state of AT has been recognized as a factor in resistance to weight loss in obese subjects. Fibrosis is also associated with metabolic complications. These alterations are mainly due to the development of a rigid matricial network surrounding the adipocytes and exerting mechanical forces on them (Pellegrinelli et al. 2014).
The objective of this project was to develop an innovative in vitro 3D model mimicking these deleterious effects of this fibrotic microenvironment on the metabolism of human mature adipocytes. To do so, we first isolated the two main components of the 3D model, which were human mature adipocytes (MA) from abdominal dermolipectomy of non-obese women using an enzymatic digestion, and native fibres of extracellular matrix collected from AT of obese women. These native fibres underwent a decellularization process to remove all cell types present in the matrix. Then, we incorporated the MA and the decellularized fibres into a biocompatible hydrogel to create capsules that we named “Fibro- Caps”. Once the model was created, cytotoxicity and lipolytic activity were assessed by colorimetric assay. Cytotoxicity by measuring the activity of the lactate dehydrogenase (LDH) released by suffering cells, and lipolysis activity by comparing basal and isoproterenol stimulated glycerol released in culture medium. Thereafter, the endocrine function of the MA was assessed by determining concentrations of adiponectin and interleukin 6 (IL-6) using an enzyme linked immunosorbent assay (ELISA) in culture media. Last, we determined cells roughness and rigidity thanks to atomic force microscope (AFM) technology.
The results showed that, although higher compared to control adipocytes without fibres, particularly on day 8, the activity of lactate dehydrogenase (LDH) in MA cultured under fibrotic condition remained below the acceptability threshold of 20%. In addition, we observed the same metabolic disruption of human fibrotic state for the parameters. Indeed, under fibrotic condition, the response of MA to a lipolytic stimulus was altered, resulting in a decrease of glycerol release fold between isoproterenol and basal condition. Moreover, we observed an inflammatory response characterized by an increase in secretion of the proinflammatory cytokine IL-6 and a decrease in adiponectin secretion which is an adipokine with insulin-sensitive and anti-inflammatory properties. Finally, AFM showed a higher roughness and rigidity for MA with fibres.
In the end, the encapsulation of human MA with native matrix fibres induced the same metabolic alterations that can be observed in cellulite, obese or aged AT, namely a resistance to lipolysis stimulation and the development of an inflammatory state. We also observed changes in the cell membrane property that could be linked to an increase of the mechanical pressure applied to them and thus to the stress they undergo.
References :
Pellegrinelli V, Heuvingh J, du Roure O, Rouault C, Devulder A, Klein C, Lacasa M, Clément E, Lacasa D, Clément K. Human adipocyte function is impacted by mechanical cues. J Pathol. 2014 Jun;233(2):183-95. doi: 10.1002/path.4347. PMID: 24623048.
Léopold Devineaux, Marion Bourdens, Danièle Lacasa and Mayoura Kéophiphath
DIVA Expertise, 1 Place Pierre Potier, 31100 Toulouse, France
During cellulite, obesity or aging, immune cells can accumulate in adipose tissue (AT) contributing to the development of a local and low grade inflammation. Chronicization of this inflammatory state can lead to an intense remodelling of extracellular matrix that can be qualified as fibrosis. Clinically, this fibrotic state of AT has been recognized as a factor in resistance to weight loss in obese subjects. Fibrosis is also associated with metabolic complications. These alterations are mainly due to the development of a rigid matricial network surrounding the adipocytes and exerting mechanical forces on them (Pellegrinelli et al. 2014).
The objective of this project was to develop an innovative in vitro 3D model mimicking these deleterious effects of this fibrotic microenvironment on the metabolism of human mature adipocytes. To do so, we first isolated the two main components of the 3D model, which were human mature adipocytes (MA) from abdominal dermolipectomy of non-obese women using an enzymatic digestion, and native fibres of extracellular matrix collected from AT of obese women. These native fibres underwent a decellularization process to remove all cell types present in the matrix. Then, we incorporated the MA and the decellularized fibres into a biocompatible hydrogel to create capsules that we named “Fibro- Caps”. Once the model was created, cytotoxicity and lipolytic activity were assessed by colorimetric assay. Cytotoxicity by measuring the activity of the lactate dehydrogenase (LDH) released by suffering cells, and lipolysis activity by comparing basal and isoproterenol stimulated glycerol released in culture medium. Thereafter, the endocrine function of the MA was assessed by determining concentrations of adiponectin and interleukin 6 (IL-6) using an enzyme linked immunosorbent assay (ELISA) in culture media. Last, we determined cells roughness and rigidity thanks to atomic force microscope (AFM) technology.
The results showed that, although higher compared to control adipocytes without fibres, particularly on day 8, the activity of lactate dehydrogenase (LDH) in MA cultured under fibrotic condition remained below the acceptability threshold of 20%. In addition, we observed the same metabolic disruption of human fibrotic state for the parameters. Indeed, under fibrotic condition, the response of MA to a lipolytic stimulus was altered, resulting in a decrease of glycerol release fold between isoproterenol and basal condition. Moreover, we observed an inflammatory response characterized by an increase in secretion of the proinflammatory cytokine IL-6 and a decrease in adiponectin secretion which is an adipokine with insulin-sensitive and anti-inflammatory properties. Finally, AFM showed a higher roughness and rigidity for MA with fibres.
In the end, the encapsulation of human MA with native matrix fibres induced the same metabolic alterations that can be observed in cellulite, obese or aged AT, namely a resistance to lipolysis stimulation and the development of an inflammatory state. We also observed changes in the cell membrane property that could be linked to an increase of the mechanical pressure applied to them and thus to the stress they undergo.
References :
Pellegrinelli V, Heuvingh J, du Roure O, Rouault C, Devulder A, Klein C, Lacasa M, Clément E, Lacasa D, Clément K. Human adipocyte function is impacted by mechanical cues. J Pathol. 2014 Jun;233(2):183-95. doi: 10.1002/path.4347. PMID: 24623048.
MicroRNAs from dietary plants could modulate human genes involved in inflammation and obesity physiopathology
Ester Díez-Sainz 1*, Silvia Lorente-Cebrián 2,3,4, Paula Aranaz 1,5, José I Riezu-Boj 1,5 and Fermín I Milagro 1,5,6
1 Department of Nutrition, Food Science and Physiology/Center for Nutrition Research, Faculty of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain.
2 Department of Pharmacology, Physiology and Legal and Forensic Medicine, Faculty of Health and Sport Science, University of Zaragoza, Zaragoza, Spain.
3 Instituto Agroalimentario de Aragón-IA2, Universidad de Zaragoza-CITA, Zaragoza, Spain.
4 Aragón Health Research Institute (IIS-Aragon), Zaragoza, Spain.
5 Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
6 Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain. * Correspondence: [email protected]
Background: Long-term exacerbated inflammation contributes to obesity progression and promotes the development of several comorbidities, such as cardiovascular diseases, diabetes and fatty liver [1]. Plants could exert anti-inflammatory and antioxidant activities, being effective in the treatment of obesity complications [2]. Plant microRNAs (miRNAs) are emerging as cross-kingdom gene expression regulators and could be key bioactive functional molecules of food origin [3,4]. However, the direct impact of plant miRNAs in obesity-related inflammation has not been explored yet.
Objective: The objective of the present work is to identify dietary plant miRNAs that can modulate the expression of pro-inflammatory human genes involved in obesity physiopathology.
Methods: RNA was isolated from edible plants and conserved miRNAs were identified by NGS (small RNA-seq) in several food matrices. A bioinformatics analysis was performed to predict human target genes involved in inflammation of the most abundantly expressed plant miRNAs. Functional validation was carried out in human THP-1 cells differentiated to macrophages where expression of target genes and their biological impact was analyzed.
Results: ppe-miRNA482f is conserved and abundantly present in several types of nuts, fruits and legumes. Transfection of this miRNA (for 48 h) inhibited the expression of putative targets NFAM1 and CLEC7A by 30% in human macrophages. In addition, transfection of human macrophages with ppe-miRNA482f also down-regulated the expression of the pro-inflammatory genes TLR6 and TNF and up-regulated anti-inflammatory IL10.
Conclusions: ppe-miRNA482f is present in edible plants and is able to modulate the expression of inflammation-related genes through the direct downregulation of NFAM1 and CLEC7A. The inhibition of CLEC7A has been previously associated with diet-induced obesity protection [5]. Therefore, miRNA ppe-miRNA482f might be an underlying mechanism by which certain plant foods may counteract systemic inflammation during obesity, and thus it could be a potential therapeutic target to treat obesity and inflammatory diseases.
This project is supported by CIBERobn (CB12/03/30002), MICINN (RTI2018-102205-B-I00 project) and a Center for Nutrition Research (UNAV) predoctoral grant.
References:
- Artemniak-Wojtowicz D et al. Obesity and chronic inflammation crosslinking. Cent Eur J Immunol. 2020;45(4):461-468. doi: 10.5114/ceji.2020.103418.
- Gamboa-Gómez CI et al. Plants with potential use on obesity and its complications. EXCLI J. 2015;14:809-31. doi: 10.17179/excli2015-186.
- Díez-Sainz E et al. Potential Mechanisms Linking Food-Derived MicroRNAs, Gut Microbiota and Intestinal Barrier Functions in the Context of Nutrition and Human Health. Front Nutr. 2021;8:586564. doi: 10.3389/fnut.2021.586564.
- Zhang L et al. Dietary microRNA-A Novel Functional Component of Food. Adv Nutr. 2019;10(4):711-721. doi: 10.1093/advances/nmy127.
- Castoldi A et al. Dectin-1 Activation Exacerbates Obesity and Insulin Resistance in the Absence of MyD88. Cell Rep. 2017;19(11):2272-2288. doi: 10.1016/j.celrep.2017.05.059.
Pterostilbene and resveratrol effects on brown adipose tissue metabolism
Iker Gómez García 1, Jenifer Trepiana 1,2, Alfredo Fernández-Quintela 1,2, María Puy Portillo 1,2
1 Nutrition and Obesity group, Department of Pharmacy and Food Sciences, Faculty of Pharmacy, University of the Basque Country (UPV/EHU) and Lucio Lascaray Research Centre, Vitoria, Spain. Email: [email protected]
2 CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Institute of Health Carlos III, Spain
Introduction: The recruitment and activation of interscapular brown adipose tissue (iBAT) could counteract the development of obesity and its co-morbidities. Although the main activators of iBAT are cold and adrenergic stimulation, certain bioactive compounds could also have this capacity. Therefore, pterostilbene, a dimethoxy derivative of resveratrol has emerged as a useful tool for the prevention and treatment of obesity due to its higher bioavailability compared to resveratrol. Objective: The aim of this study was to analyse the capacity of pterostilbene and resveratrol to act on the metabolism of iBAT from rats fed an obesogenic diet. Methods: Rats were distributed into 5 experimental groups and fed either a standard or a high-fat high-fructose (HFHF) diet, supplemented or not with pterostilbene (15 or 30 mg/kg/day) or resveratrol (30 mg/kg/day) for 8 weeks. Triglyceride levels were measured spectrophotometrically, and protein expression of uncoupling protein 1 (UCP1), glucose transporter type 4 (GLUT4), mitochondrial transcription factor A (TFAM) and sirtuin 3 (SIRT3) were measured by immunoblotting. Results: Regarding iBAT weight, no changes were observed among groups. Nevertheless, the HFHF diet caused a significantly rise in triglyceride levels in this tissue. With regard to the mechanism of action, differences were not observed in UCP1, GLUT4, TFAM and SIRT3 protein expression between the HFHF and the control groups. Interestingly, pterostilbene (both doses) and resveratrol prevented the increase in triglycerides caused by the obesogenic diet. Resveratrol group showed an increase in both UCP1 and SIRT3 protein expression when treated rats were compared with rats fed a HFHF diet. Pterostilbene prompted a significant increase in UCP1 protein expression compared with the control group. Nevertheless, no changes mediated by phenolic compounds in GLUT4 or TFAM protein expression were found. Conclusions: In IBAT, pterostilbene and resveratrol enhanced thermogenic capacity, and both were able to completely prevent the triglyceride raise induced by the HFHF diet, process mediated, at least in part, by an increase in thermogenic capacity.
This project is supported by the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional, grant number AGL-2015-65719-R MINECO/FEDER, (UE); the Instituto de Salud Carlos III (CIBERobn), grant number CB12/03/ 30007; the University of the Basque Country, grant number GIU 18/173; and the Instituto de Salud Carlos III(CIBERehd).
Iker Gómez García 1, Jenifer Trepiana 1,2, Alfredo Fernández-Quintela 1,2, María Puy Portillo 1,2
1 Nutrition and Obesity group, Department of Pharmacy and Food Sciences, Faculty of Pharmacy, University of the Basque Country (UPV/EHU) and Lucio Lascaray Research Centre, Vitoria, Spain. Email: [email protected]
2 CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Institute of Health Carlos III, Spain
Introduction: The recruitment and activation of interscapular brown adipose tissue (iBAT) could counteract the development of obesity and its co-morbidities. Although the main activators of iBAT are cold and adrenergic stimulation, certain bioactive compounds could also have this capacity. Therefore, pterostilbene, a dimethoxy derivative of resveratrol has emerged as a useful tool for the prevention and treatment of obesity due to its higher bioavailability compared to resveratrol. Objective: The aim of this study was to analyse the capacity of pterostilbene and resveratrol to act on the metabolism of iBAT from rats fed an obesogenic diet. Methods: Rats were distributed into 5 experimental groups and fed either a standard or a high-fat high-fructose (HFHF) diet, supplemented or not with pterostilbene (15 or 30 mg/kg/day) or resveratrol (30 mg/kg/day) for 8 weeks. Triglyceride levels were measured spectrophotometrically, and protein expression of uncoupling protein 1 (UCP1), glucose transporter type 4 (GLUT4), mitochondrial transcription factor A (TFAM) and sirtuin 3 (SIRT3) were measured by immunoblotting. Results: Regarding iBAT weight, no changes were observed among groups. Nevertheless, the HFHF diet caused a significantly rise in triglyceride levels in this tissue. With regard to the mechanism of action, differences were not observed in UCP1, GLUT4, TFAM and SIRT3 protein expression between the HFHF and the control groups. Interestingly, pterostilbene (both doses) and resveratrol prevented the increase in triglycerides caused by the obesogenic diet. Resveratrol group showed an increase in both UCP1 and SIRT3 protein expression when treated rats were compared with rats fed a HFHF diet. Pterostilbene prompted a significant increase in UCP1 protein expression compared with the control group. Nevertheless, no changes mediated by phenolic compounds in GLUT4 or TFAM protein expression were found. Conclusions: In IBAT, pterostilbene and resveratrol enhanced thermogenic capacity, and both were able to completely prevent the triglyceride raise induced by the HFHF diet, process mediated, at least in part, by an increase in thermogenic capacity.
This project is supported by the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional, grant number AGL-2015-65719-R MINECO/FEDER, (UE); the Instituto de Salud Carlos III (CIBERobn), grant number CB12/03/ 30007; the University of the Basque Country, grant number GIU 18/173; and the Instituto de Salud Carlos III(CIBERehd).
Anti-obesity effect of Opuntia stricta var. Dillenii’ in 3T3-L1 mature adipocytes. A preliminary study
Ivan Gomez-Lopez 1,2,3,*, M. Pilar Cano 1, María P. Portillo 2,3,4
1 Laboratory of Phytochemistry and Plant Food Functionality, Biotechnology and Food Microbiology Department, Institute of Food Science Research (CIAL) (CSIC-UAM), Madrid, Spain.
2 Nutrition and Obesity Group, Dept of Nutrition & Food Science, Univ. of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain.
3 CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III (ISCIII), Vitoria-Gasteiz, Spain
4 BIOARABA Institute of Health, 01006 Vitoria-Gasteiz, Spain. * Email address: [email protected]
Opuntia stricta var. Dillenii’s prickly pears are fruits rich in bioactive compounds, such as betalains (betanin) and phenolic compounds: phenolic acids (pisicidic acid) and flavonoids (ishoramnetin glucoside). These phytochemicals could bring potential health benefits for humans related to obesity by their the supossed potential delipidating activity. Studies with other Opuntia spp. varieties, shuch as, Opuntia ficus-indica L. Mill, have demostrated that aqueous extracts rich in betalains, piscidic acid and isorhamnetin glycosides obtained by pricly pears could reduced triacylglycerol accumulation in 3T3-L1 mature adipocytes. The aim of the present study was to analyze the delipidating effect of the extracts from the Opuntia stricta var. Dillenii fruit tissues (whole fruit, pulp and pell) and one by-product obtained from their industrial uses (bagasse). First, the cytotoxic effect of the extracts at 10, 25, 50 and 100 μg/mL doses was evaluated. Cell viaibility did not decrease significantly, so cells were treated on day 12 after the induction of differentiation during 24 h. At 50 μg/mL extracts from whole fruit, peel and pulp showed a delipidating effect, -46.7%, -27,5% and -37.4%, respectively. Bagasse, was not able to reduced TG content in mature adipocytes.
This research was funded by the Spanish Ministry of Science and Innovation, project numbers PID2020-118300RB-C21 and PID2020-118300RB-C22 and Basque Country Government pre-doctoral scholarship.
The results demonstrate that these extracts show anti-obesity effects, but the concentration of 50 μg/mL is probably higher than that found in plasma after in vivo treatments. Nevertheless, this is a preliminar study, and new repetitions of this experiments should be performed before reaching clear conclusions.
References:
Ivan Gomez-Lopez 1,2,3,*, M. Pilar Cano 1, María P. Portillo 2,3,4
1 Laboratory of Phytochemistry and Plant Food Functionality, Biotechnology and Food Microbiology Department, Institute of Food Science Research (CIAL) (CSIC-UAM), Madrid, Spain.
2 Nutrition and Obesity Group, Dept of Nutrition & Food Science, Univ. of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain.
3 CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III (ISCIII), Vitoria-Gasteiz, Spain
4 BIOARABA Institute of Health, 01006 Vitoria-Gasteiz, Spain. * Email address: [email protected]
Opuntia stricta var. Dillenii’s prickly pears are fruits rich in bioactive compounds, such as betalains (betanin) and phenolic compounds: phenolic acids (pisicidic acid) and flavonoids (ishoramnetin glucoside). These phytochemicals could bring potential health benefits for humans related to obesity by their the supossed potential delipidating activity. Studies with other Opuntia spp. varieties, shuch as, Opuntia ficus-indica L. Mill, have demostrated that aqueous extracts rich in betalains, piscidic acid and isorhamnetin glycosides obtained by pricly pears could reduced triacylglycerol accumulation in 3T3-L1 mature adipocytes. The aim of the present study was to analyze the delipidating effect of the extracts from the Opuntia stricta var. Dillenii fruit tissues (whole fruit, pulp and pell) and one by-product obtained from their industrial uses (bagasse). First, the cytotoxic effect of the extracts at 10, 25, 50 and 100 μg/mL doses was evaluated. Cell viaibility did not decrease significantly, so cells were treated on day 12 after the induction of differentiation during 24 h. At 50 μg/mL extracts from whole fruit, peel and pulp showed a delipidating effect, -46.7%, -27,5% and -37.4%, respectively. Bagasse, was not able to reduced TG content in mature adipocytes.
This research was funded by the Spanish Ministry of Science and Innovation, project numbers PID2020-118300RB-C21 and PID2020-118300RB-C22 and Basque Country Government pre-doctoral scholarship.
The results demonstrate that these extracts show anti-obesity effects, but the concentration of 50 μg/mL is probably higher than that found in plasma after in vivo treatments. Nevertheless, this is a preliminar study, and new repetitions of this experiments should be performed before reaching clear conclusions.
References:
- Gómez-López, I., Lobo-Rodrigo, G., Portillo, M. P. & Cano, M. P. (2021, 9 july). Characterization, Stability, and Bioaccessibility of Betalain and Phenolic Compounds from Opuntia stricta var. Dillenii Fruits and Products of Their Industrialization. Foods, 10(7), 1593. https://doi.org/10.3390/foods10071593
Impact of obesity on periodontal status and response to non-surgical periodontal therapy in patients with periodontitis
Lê Sylvie* 1,2,3, Thomas Charlotte* 1,2,3, Yanat Noor 2,3, Minty Matthieu 1,2,3, Loubières Pascale 1,2,3, Canceill Thibault 1,2,3, Azalbert Vincent 1,2, Burcelin Rémy 1,2, Blasco-Baque Vincent 1,2,3, Laurencin-Dalicieux Sara 2,3. (*equal contribution).
1INSERM U1048, F-31432 Toulouse, France. Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse, France. 2Université Paul Sabatier III (UPS), F- 31432 Toulouse, France. 3CHU Toulouse, Service d’Odontologie Toulouse, France.
Introduction: Worldwide 39% of the adults are considered overweight. As in the intestine, obese people are characterized by a dysbiotic oral microbiota [1]. Periodontitis is an oral pathology also initiated by oral dysbiosis that can induce local and systemic immuno-inflammatory reactions altering cardio-metabolic diseases [2]. According to the current literature, several mechanisms support the "bi-directional" relationship between obesity and periodontitis [3]. However, the causal link between the 2 diseases remains to be found.
Objective: Evaluate the relationship between obesity and periodontitis in terms of initial periodontal status but also in the response to periodontal treatment.
Method: We conducted a study of 87 patients suffering from periodontitis. We constituted three groups of patients with periodontal disease: a group of normo-weighted patients with a BMI < 25 kg/m2 (n=49), a group of overweight patients with a 25 < BMI < 30 kg/m2 (n=28) and a group of obese patients with a BMI > 30 kg/m2 (n=10). We reported the clinical, systemic and oral microbiota parameters but also lifestyle and nutritional behavior.
Preliminary results: Some patients in the obese and overweight groups had diabetes or a pre-diabetic state, thus an additional risk factor for periodontitis. Regarding the oral status, obese patients had a greater initial loss of attachment than overweighted (5,2 ± 2,1 vs 4,9 ± 1,1, p = 0,02) or normo-weighted patients (5,2 ± 2,1 vs 4,8 ± 1,3, p = 0,04). Results of the bacterial culture show that bacterial charge in periodontal samples reveal no significant differences between the 3 groups (1,44E+07 ± 1,25E+07 vs 7,21E+06 ± 6,28E+06 vs 1,34E+07 ± 1,00E+07, p=0,08). Non-surgical periodontal therapy by root debridement improved the clinical situation in all 3 groups but to a lesser extent in the obese group. Perspective: We show that there is no difference in quantity of oral bacteria between the 3 groups. It would be interesting to describe the bacterial composition of the oral microbiota of these patients grouped according to their BMI in order to identify a difference or not of oral microbiota quality. Characterization of the whole oral microbiota using metagenomics will analyze the flora without any preconceived ideas. Increased comprehension of this periodontitis-obesity association will help develop new therapeutic strategies for the prevention and treatment of obese patients suffering from periodontitis.
References:
[1] Y. Wu, X. Chi, Q. Zhang, F. Chen, et X. Deng, « Characterization of the salivary microbiome in people with obesity », PeerJ, vol. 6, p. e4458, 2018, doi: 10.7717/peerj.4458.
[2] G. Hajishengallis, « Periodontitis: from microbial immune subversion to systemic inflammation », Nat. Rev. Immunol., vol. 15, no 1, p. 30‐44, janv. 2015, doi: 10.1038/nri3785.
[3] S. Jepsen, J. Suvan, et J. Deschner, « The association of periodontal diseases with metabolic syndrome and obesity », Periodontol. 2000, vol. 83, no 1, p. 125‐153, juin 2020, doi: 10.1111/prd.12326.
Effect of virgin olive oil as spreadable preparation on progression of atheroma plaque compared to dairy butter
in Apo-E-deficient mice
Roberto Martínez-Beamonte 1, Cristina Barranquero 1, Sonia Gascón 1, Juan Mariño 2, Carmen Arnal 1, María Jesús Rodriguez-Yoldi 1, Joaquín Carlos Surra 1, Jesús Osada 1*, María Ángeles Navarro 1
1 1CIBER de Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Instituto de Salud Carlos III, Spain. Veterinary Faculty, Zaragoza University, Miguel Servet, 177, 50013 Zaragoza, Spain. E-mail: [email protected] 2 Las arbequinas de Rosalía
Olive oil is the main source of fat-energy in the Mediterranean diet and robust evidences confirm its benefits on health. The effect of virgin olive oil in form of a spreadable preparation (S-VOO) on the progression of atheroma plaques was investigated in Apo-E-deficient mice, a model of accelerated atherosclerosis. Methods: two atherogenic and isocaloric diets based on a purified diets supplemented with 20 % of fat [1], either as a spreadable preparation of virgin olive oil or dairy butter were used to feed 28 males and 16 females of two-month old mice on ApoE-deficient background during 12 weeks. Spreadable virgin olive oil (S-VOO) was made by blending more than 75% of virgin olive oil and other natural fats obtaining a monounsaturated-enriched fat. Total plasma cholesterol, triglyceride, and HDL-cholesterol were assayed. Hepatic lipids were extracted analysed from frozen livers. Areas of aortic lesions were quantified in cross-sectional images from proximal aorta [2]. Results: Total plasma cholesterol increased significantly in mice on diet supplemented with butter as well in female as male mice compared with S-VOO, and HDL-cholesterol was significantly higher in S-VOO than in butter diet although only in males, and no differences in plasma triglycerides were observed. Likewise, no significant differences in hepatic lipids were observed between diets in either sex. Aortic lesions areas were significantly higher in mice consuming butter diet than S-VOO in both sexes. Conclusion: virgin olive oil consumed in spreadable form maintained the same healthy properties, delaying the progression of atheroma plaque as its original liquid state.
This project is supported by Ibercaja technology check “Innovación sólida para el aceite de oliva virgen extra” and CIBERobn (Unizar).
References:
- Martínez-Beamonte R, Alda O, Sanclemente T, Felices MJ, Escusol S, Arnal C, Herrera-Marcos LV, Gascón S, Surra JC, Osada J, Rodríguez-Yoldi MJ. Hepatic subcellular distribution of squalene changes according to the experimental setting. J Physiol Biochem. 2018 Nov;74(4):531-538. doi: 10.1007/s13105-018-0616-2. Epub 2018 Feb 22.
- Herrera-Marcos LV, Sancho-Knapik S, Gabás-Rivera C, Barranquero C, Gascón S, Romanos E, Martínez-Beamonte R, Navarro MA, Surra JC, Arnal C, García-de-Jalón JA, Rodríguez-Yoldi MJ, Tena-Sempere M, Sánchez-Ramos C, Monsalve M, Osada J. Pgc1a is responsible for the sex differences in hepatic Cidec/Fsp27β mRNA expression in hepatic steatosis of mice fed a Western diet. Am J Physiol Endocrinol Metab. 2020 Feb 1;318(2):E249-E261. doi: 10.1152/ajpendo.00199.2019. Epub 2019 Dec 17.
Study of altered hormone expression in obese subjects related to appetite and satiety signaling
Jesica Martínez Godfrey 1*, Enrique Roche 1,2, Vicente Micol 1,2 and María Herranz-López 1
1 Instituto de Biología Molecular y Celular, Universidad Miguel Hernández de Elche, Alicante, Spain.
2 CIBER, Fisiopatología de la Obesidad y la Nutrición, CIBERobn, Instituto de Salud Carlos III (CB12/03/30038). Spain.
Obesity is a disease that has currently reached epidemic levels. The prevalence of this disease is still rising and, if the trend continues, prevalence worldwide will reach 18% in men and 21% in women by 20251. The metabolic stress associated with obesity is an important risk factor for the development of several metabolic dysfunctions such as hypertension, type 2 diabetes, cardiovascular diseases and even cancer2. Existing pharmacological treatments against obesity are not completely effective and are associated with certain side effects, so the combination of calorie restriction and physical exercise seems to be the only effective strategy. However, caloric restriction results in a compensatory response in the hypothalamus, which regulates and integrates hormonal signals related to appetite and satiety, generating the secretion of orexigenic hormones and increasing the sensation of appetite to restore energy homeostasis3. On the other hand, preliminary trials of brain activity recordings through neuroimaging have postulated that successful long-term weight loss maintainers have an hyperactivated pattern in the lateral prefrontal cortex in response to food signals4.
The global aim of this Project is to identify the cortical brain regions involved in appetite/satiety to perform safe and transcranial direct current stimulation (tDCS) with the purpose of inducing a pattern corresponding to satiety sensation and correlate it to circulating anorexigenic hormones in obese subjects. Consequently, the main objective of the present study was to stablish as valid the Luminex technology to determine plasmatic hormone concentrations and to correlate their values with the body mass and plasmatic glucose levels in the volunteers studied.
Our preliminary results through a pilot trial in 6 obese and/or hyperphagic subjects and one normoweight control show alterations in the concentrations of hormones related to the appetite/saciety modulation, namely, insulin, GLP-1, leptin and resistin, among others.
These early results constitute a base to continue studying the anorexigenic hormone secretion in obesity in order to tackle the appetite and satiety signaling mechanisms altered in obesity.
This work is supported by the Project PROMETEO/2021/059 from Generalitat Valenciana and The Spanish Ministry of Economy and Competitiveness (MINECO, Project RTI2018-096724-B-C21 and PID2021-125188OB-C31).
References:
Jesica Martínez Godfrey 1*, Enrique Roche 1,2, Vicente Micol 1,2 and María Herranz-López 1
1 Instituto de Biología Molecular y Celular, Universidad Miguel Hernández de Elche, Alicante, Spain.
2 CIBER, Fisiopatología de la Obesidad y la Nutrición, CIBERobn, Instituto de Salud Carlos III (CB12/03/30038). Spain.
Obesity is a disease that has currently reached epidemic levels. The prevalence of this disease is still rising and, if the trend continues, prevalence worldwide will reach 18% in men and 21% in women by 20251. The metabolic stress associated with obesity is an important risk factor for the development of several metabolic dysfunctions such as hypertension, type 2 diabetes, cardiovascular diseases and even cancer2. Existing pharmacological treatments against obesity are not completely effective and are associated with certain side effects, so the combination of calorie restriction and physical exercise seems to be the only effective strategy. However, caloric restriction results in a compensatory response in the hypothalamus, which regulates and integrates hormonal signals related to appetite and satiety, generating the secretion of orexigenic hormones and increasing the sensation of appetite to restore energy homeostasis3. On the other hand, preliminary trials of brain activity recordings through neuroimaging have postulated that successful long-term weight loss maintainers have an hyperactivated pattern in the lateral prefrontal cortex in response to food signals4.
The global aim of this Project is to identify the cortical brain regions involved in appetite/satiety to perform safe and transcranial direct current stimulation (tDCS) with the purpose of inducing a pattern corresponding to satiety sensation and correlate it to circulating anorexigenic hormones in obese subjects. Consequently, the main objective of the present study was to stablish as valid the Luminex technology to determine plasmatic hormone concentrations and to correlate their values with the body mass and plasmatic glucose levels in the volunteers studied.
Our preliminary results through a pilot trial in 6 obese and/or hyperphagic subjects and one normoweight control show alterations in the concentrations of hormones related to the appetite/saciety modulation, namely, insulin, GLP-1, leptin and resistin, among others.
These early results constitute a base to continue studying the anorexigenic hormone secretion in obesity in order to tackle the appetite and satiety signaling mechanisms altered in obesity.
This work is supported by the Project PROMETEO/2021/059 from Generalitat Valenciana and The Spanish Ministry of Economy and Competitiveness (MINECO, Project RTI2018-096724-B-C21 and PID2021-125188OB-C31).
References:
- Di Cesare, M., et al., Trends in adult body-mass index in 200 countries from 1975 to 2014: A pooled analysis of 1698 population-based measurement studies with 19.2 million participants. The Lancet, 2016. 387, 1377–1396.
- Engin A. The Definition and Prevalence of Obesity and Metabolic Syndrome. Adv Exp Med Biol. 2017;960:1-17. doi: 10.1007/978-3-319-48382-5_1. PMID: 28585193.
- Busetto L, Bettini S, Makaronidis J, Roberts CA, Halford JCG, Batterham RL. Mechanisms of weight regain. Eur J Intern Med. 2021 Nov;93:3-7. doi: 10.1016/j.ejim.2021.01.002. Epub 2021 Jan 16. PMID: 33461826.
- Stoeckel, L. E. et al. Psychological and neural contributions to appetite self-regulation. Obesity (Silver Spring) 25 Suppl 1, S17 S25, doi:10.1002/oby.21789 (2017).
Antidiabetic and anti-obesity properties of comercial and autocthonous apple pulp extracts (Malus domestica Borkh)
Adrián Millán-Laleona a*, Sonia Núñez a, Francisco Les a,b, Carlota Gómez-Rincón a,b, Víctor López a,b
a Faculty of Health Sciences, Universidad San Jorge, 50830 Villanueva de Gállego (Zaragoza), Spain
b Instituto Agroalimentario de Aragón, IA2, Universidad de Zaragoza-CITA*[email protected]
Apples are fruits of great agricultural and economic interest in Europe, being also highly appreciated for its nutritional value and its association with several health benefits. The largest amount of apple consumed in Spain corresponds to commercial and imported varieties, losing some autochthonous genotypes well adapted to our climate and geography. Some studies suggest that its consumption produces a decrease in the risk of suffering cardiovascular diseases and diabetes, which could be related to the presence of polyphenols and other phytochemicals that are naturally found in the fruit. Polyphenols have antioxidant and antiglycan properties, preventing oxidative stress and cell aging associated with many pathologies.
The aim of this project is to evaluate the antioxidant, antidiabetic, and anti-obesity effects of pulp apple extracts through in vitro and in vivo assays. The fruits tested come from one commercial apple variety (Pinova) and a local apple grown in a mountainous area of Aragón. The extraction of bioactive compounds was achieved by using methanol as solvent and ultrasonication.
Considering the chemical assays, total quantity of polyphenols was determined using the Folin method. To determine the antioxidative properties, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical assay was performed and the inhibition of xanthine oxidase was tested for a better understanding of the antioxidant capacity of the extracts. To evaluate the antidiabetic and anti-obesity potential, we analyzed the inhibition of advanced glycation end products (AGEs) production using albumin bovine serum and fructose as well as the inhibition of the enzymes α-glucosidase and pancreatic lipase. Additionally, Caenorhabditis elegans (C. elegans) was used as an in vivo model to assess the extracts toxicity and their abilities to interfere with the accumulation of lipid droplets in the worm.
The results of the local variety stand out against the commercial one. The local variety shows better antioxidant, antidiabetic, and anti-obesity properties than the Pinova pulp extract, being three times higher the total polyphenol content. The local variety was also able to inhibit α-glucosidase in a dose-dependent manner similar to the drug acarbose. This study reveals that the autochthonous variety may contain interesting polyphenols with nutritional and biological health benefits.
Acknowledgments: APPLECUT project (ref. PID2019-108081RR-C21), financed by the 2019 call of the Ministry of Science and Innovation oriented to societal challenges. To the Government of Aragon for the financing of the Phyto-Pharm group (ref. B44_20D).
References:
- Yu, C. H. J., Migicovsky, Z., Song, J., & Rupasinghe, H. P. V. (2022). (Poly)phenols of apples contribute to in vitro antidiabetic properties: Assessment of Canada's Apple Biodiversity Collection. Plants, People, Planet, 1– 16. https://doi.org/10.1002/ppp3.1031
- López et al., 2007. In vitro antioxidant and anti-rhizopus activities of Lamiaceae herbal extracts. Plant Foods Hum Nutr. 2007 Dec;62(4):151-5
- Spinola et al (2017). Evaluation of Asteraceae herbal extracts in the management of diabetes and obesity. Contribution of caffeoylquinic acids on the inhibition of digestive enzymes activity and formation of advanced glycation end-products (in vitro). Phytochemistry. 2017 Nov;143:29-35.
Isoliquiritigenin in combination with visceral adipose tissue and related markers as a predictive tool for Non-Alcoholic Fatty Liver Disease
Paola Mogna-Peláez 1, Ana Romo-Hualde 1, David Muñoz-Prieto 1, José I. Riezu-Boj 1,2, Fermín I. Milagro 1,2,3 Mariana Elorz 2,4, Alberto Benito-Boillos 2,4, José I. Herrero 2,5,6, J. Ignacio Monreal 7, Josep A. Tur 3,8, J. Alfredo Martínez 1, Itziar Abete 1,2,3, M. Ángeles Zulet 1,2,3.
1 Department of Nutrition, Food Sciences and Physiology and Centre for Nutrition Research, Faculty of Pharmacy and Nutrition, Centre for Nutrition Research, University of Navarra, 31008 Pamplona, Spain.
2 Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain.
3Biomedical Res. Centre Network in Physiopathology of Obesity and Nutrition (CIBERobn), Inst. de Salud Carlos III, Madrid, Spain.
4 Department of Radiology, Clínica Universidad de Navarra, 31008 Pamplona, Spain.
5 Liver Unit, Clínica Universidad de Navarra, 31008 Pamplona, Spain.
6 Biomedical Research Centre Network in Hepatic and Digestive Diseases (CIBERehd), 28029 Madrid, Spain.
7 Clinical Chemistry Department, Clínica Universidad de Navarra, 31008 Pamplona, Spain.
8 Research Group on Community Nutrition and Oxidative Stress, University of Balearic Islands, 07122 Palma, Spain
[email protected] and [email protected]
Background and Aims: Non-Alcoholic Fatty Liver Disease (NAFLD) is the most prevalent form of chronic liver disease in the world (1). New non-invasive diagnostic tools are needed to promptly treat this disease and avoid its complications (2). This study aimed to find key metabolites and related variables that could be used to predict and diagnose NAFLD (3,4).
This research was funded by the Health Department of the Government of Navarra, with the FLiO (Ref. 61/2015) and EHGNA (PC082-083-084) projects, CIBERobn (Physiology of Obesity and Nutrition, CB12/03/30002), and the Centre for Nutrition Research (CIN) of the University of Navarra.
References:
Paola Mogna-Peláez 1, Ana Romo-Hualde 1, David Muñoz-Prieto 1, José I. Riezu-Boj 1,2, Fermín I. Milagro 1,2,3 Mariana Elorz 2,4, Alberto Benito-Boillos 2,4, José I. Herrero 2,5,6, J. Ignacio Monreal 7, Josep A. Tur 3,8, J. Alfredo Martínez 1, Itziar Abete 1,2,3, M. Ángeles Zulet 1,2,3.
1 Department of Nutrition, Food Sciences and Physiology and Centre for Nutrition Research, Faculty of Pharmacy and Nutrition, Centre for Nutrition Research, University of Navarra, 31008 Pamplona, Spain.
2 Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain.
3Biomedical Res. Centre Network in Physiopathology of Obesity and Nutrition (CIBERobn), Inst. de Salud Carlos III, Madrid, Spain.
4 Department of Radiology, Clínica Universidad de Navarra, 31008 Pamplona, Spain.
5 Liver Unit, Clínica Universidad de Navarra, 31008 Pamplona, Spain.
6 Biomedical Research Centre Network in Hepatic and Digestive Diseases (CIBERehd), 28029 Madrid, Spain.
7 Clinical Chemistry Department, Clínica Universidad de Navarra, 31008 Pamplona, Spain.
8 Research Group on Community Nutrition and Oxidative Stress, University of Balearic Islands, 07122 Palma, Spain
[email protected] and [email protected]
Background and Aims: Non-Alcoholic Fatty Liver Disease (NAFLD) is the most prevalent form of chronic liver disease in the world (1). New non-invasive diagnostic tools are needed to promptly treat this disease and avoid its complications (2). This study aimed to find key metabolites and related variables that could be used to predict and diagnose NAFLD (3,4).
- Ninety-eight subjects with NAFLD and forty-five controls from the Fatty Liver in Obesity (FLiO) Study (NCT03183193) were analyzed (5). NAFLD was diagnosed and graded by ultrasound, and later classified into two groups: 0 (controls) and ≥ 1 (NAFLD). Hepatic status was additionally assessed through Magnetic Resonance Imaging (MRI), elastography, and determination of transaminases. Anthropometry, body composition (DXA), biochemical parameters, and lifestyle were evaluated as well (4). Non-targeted metabolomics of serum was performed with high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS). Individuals were then divided into tertiles according to Isoliquiritigenin intensity (T1, T2, and T3).
- The NAFLD subjects presented a significantly worse hepatic and metabolic status compared with controls. Metabolomic analyses revealed that Isoliquiritigenin had the strongest association with NAFLD out of the determinant metabolites established between both groups. Isoliquiritigenin was significantly correlated with hepatic, body composition and insulin resistance (IR) markers as well. Tertile divisions according to Isoliquiritigenin concentrations exhibited that individuals with higher concentrations of this metabolite had overall healthier metabolic and hepatic status. Multivariate logistic regressions and Receiver Operating Characteristic (ROC) curves demonstrated the predictive power of Isoliquiritigenin in panel combination with other NAFLD and IR related variables, such as visceral adipose tissue (VAT), plasmatic glucose, adiponectin, and CK18-M30.
- Metabolites such as Isoliquiritigenin, in combination with other NAFLD and IR associated factors, constitute a potential non-invasive tool to predict and diagnose NAFLD.
This research was funded by the Health Department of the Government of Navarra, with the FLiO (Ref. 61/2015) and EHGNA (PC082-083-084) projects, CIBERobn (Physiology of Obesity and Nutrition, CB12/03/30002), and the Centre for Nutrition Research (CIN) of the University of Navarra.
References:
- Younossi Z, Corey K, Lim J. Gastroenterology. 2021;160(3):912-918.
- Lazarus J, Mark H, Anstee Q, Arab JP, Batterham R et al. Nat Rev Gastroenterol Hepatol. 2022; 19(1): 60-78.
- Masoodi M, Gastaldelli A, Hyötyläinen T, Arretxe E, Alonso C et al. Nat Rev Gastroenterol Hepatol. 2021; 18(12): 835-856.
- Li W, Zhang L, Liu Y, Wang C, Long W et al. J Physiol Biochem. 2020; 76(4): 587-598.
- Marin-Alejandre BA, Cantero I, Perez-Diaz-Del-Campo N, Monreal JI, Elorz M et al. Liver Int. 2021; 41(7):1532-1544
Redefining the intracellular final effectors of verbascoside that alleviate glucotoxicity-induced oxidative stress in hypertrophic adipocytes
Mariló Olivares-Vicente 1, Noelia Sánchez-Marzo 1, Vicente Micol 1,2*, María Herranz-López 1*.
1 Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche, Universidad Miguel Hernández (UMH), 03202 Elche, Spain.
2 CIBER: CB12/03/30038, Fisiopatología de la Obesidad y la Nutrición, CIBERobn, Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain.
*These authors shared author co-seniorship.
Introduction: Verbascoside, the most abundant compound in lemon verbena leaves, is a phenylpropanoid with a strong antioxidant power that reduces oxidative stress associated with obesity [1, 2]. However, it is unknown whether this compound accumulates in adipocytes and which are the final antioxidant effectors that interact with intracellular targets.
Objective: The objective of this study was to understand how verbascoside is taken up by hypertrophic 3T3-L1 adipocytes and to identify the intracellular metabolites responsible for reducing oxidative stress.
Methods: The intracellular metabolites were identified and quantified by HPLC-DAD-ESI-IT-MS and correlated with intracellular ROS levels using the fluorogenic dye H2DCFDA.
Results: Verbascoside was rapidly absorbed by hypertrophic adipocytes and underwent isomerization, methylation and acetylation reactions. The decrease in oxidative stress correlated mainly, but not exclusively, with the intracellular appearance of the parent compound.
Conclusions: This study offers a better understanding of the potential molecular mechanism of verbascoside in adipose tissue and its role in ameliorating obesity-induced oxidative stress.
This work is supported by the Project PROMETEO/2021/059 from Generalitat Valenciana and The Spanish Ministry of Economy and Competitiveness (MINECO, Project RTI2018-096724-B-C21 and PID2021-125188OB-C31).
References:
- Herranz-López, M., et al., Lemon verbena (Lippia citriodora) polyphenols alleviate obesity-related disturbances in hypertrophic adipocytes through AMPK-dependent mechanisms. Phytomedicine, 2015. 22(6): p. 605-14.
- Quirantes-Pine, R., et al., Phenylpropanoids and their metabolites are the major compounds responsible for blood-cell protection against oxidative stress after administration of Lippia citriodora in rats. Phytomedicine, 2013. 20(12): p. 1112-8.
Identification of natural compounds that alleviate obesity-disturbances in human adipocytes
Irene Concepción Pomares-Bri 1, Enrique Roche 1,2, Vicente Micol 1,2, María Herranz-López 1
1 Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche, Miguel Hernández University, Alicante, Spain.
2 CIBER, Fisiopatología de la Obesidad y la Nutrición, CIBERobn, Instituto de Salud Carlos III (CB12/03/30038), Spain.
Recent studies show that polyphenols are able to modulate the metabolism contributing to alleviate obesity and its related disturbances. These data suggest that phenolic compounds can be a promising alternative as obesity treatments1. However, the study of their effects in human models is limited.
The objective of this project is to select polyphenols derived from plant extracts that show beneficial effects on the Simpson-Golabi-Behmel syndrome (SGBS) cell line2 as hypertrophic adipocytes induced by glucotoxicity conditions.
The initial aim was to study the SGBS cell line as a human obesity model on oxidative stress and triglyceride accumulation to evaluate previously selected polyphenols. For that, specific fluorescent probes for reactive oxygen species and triglycerides were used. Further, proteins expression such as AMP-activated protein kinase (AMPK) that regulate energy metabolism were detected and measured by Western Blot experiments.
Our results showed that SGBS adipocytes present higher triglyceride levels and oxidative stress in glucotoxicity conditions as in obesity, so it could be a useful model to characterize the pathways modulated by phenolic compounds. In addition, our experiments revealed that polyphenols such as ferulic acid and homoprotocatechuic acid could reduce the levels of triglycerides and reactive oxygen species similar to non-toxicity conditions. Moreover, they were able to modulate the protein expression of key targets. In conclusion, the obtained results postulate SGBS hypertrophic adipocytes as an interesting tool to perform screening of compounds and learn about their mode of action in humans.
This work was supported by the Project PROMETEO/2021/059 from Generalitat Valenciana and The Spanish Ministry of Economy and Competitiveness (MINECO, Project RTI2018-096724-B-C21 and PID2021-125188OB-C31).
References:
- Singh, M., Thrimawithana, T., Shukla, R. & Adhikari, B. Managing obesity through Natural Polyphenols: a review. Future Foods (2020).
- Wabitsch, M. et al. Characterization of a human preadipocyte cell strain with high capacity for adipose differentiation. International journal of obesity and related metabolic disorders: journal of the International Association for the Study of Obesity 25, 8-15, doi:10.1038/sj.ijo.0801520 (2001).
Reduction of obesity and insulin resistance through dual targeting of VAT and BAT by a novel combination of metabolic cofactors in diet-induced obese mice
Sergio Quesada-Vázquez 1, Anna Antolín 1, Marina Colom-Pellicer 2, Gerard Aragonès 2, Laura Herrero 3, Josep Maria Del Bas 4, Antoni Caimari 4, Xavier Escoté 1*
1 Eurecat, Technology Centre of Catalunya, Nutrition and Health Unit, 43204 Reus, Spain;
2 Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, Tarragona, Spain
3 Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Universitat de Barcelona
4 Eurecat, Centre Tecnològic de Catalunya, Biotechnology Area, Reus, Spain.
* Correspondence: [email protected]; Tel.: +34-977-302057 (ext. 4824)
Introduction: Obesity is an epidemic worldwide disease characterized by excessive fat accumulation associated with several metabolic perturbations, such as metabolic syndrome, insulin resistance, hypertension, and dyslipidemia. Prior studies have described how different bioactive co-factors related to GSH and NAD+ metabolism, separately can modulate metabolic pathways and improve white adipose tissue dysfunction in preclinical models.
Objectives: The objective of this study is to reduce pathological features of obesity by a specific combination of metabolic cofactors (MC) (betaine, N-acetylcysteine, L-carnitine, and nicotinamide riboside) as a promising treatment in a high-fat diet (HFD) mice model. The aims of the current study are:
- To reduce body weight and fat depots with an improvement in lipid oxidation linked to a better biochemical profile and respiratory index in obese diet-induced mice.
- To ameliorate adipose tissue dysfunction and adipocyte hypertrophy observed in the diet-induced obese mice model improving lipolysis and fatty acid oxidation pathways in obese diet-induced mice.
- To promote an improved glucose and insulin baseline profile. Moreover, To validate the amelioration of IR, key gene expression in insulin-dependent glucose uptake and tolerance tests are performed.
- To investigate the role of MC combination in brown adipose tissue (BAT) and its capacity to activate lipolysis, lipid oxidation, and thermogenesis pathways to reduce fat accumulation.
Results and conclusions: We demonstrated in this study that MC supplementation confers a moderate reduction of obesity and adiposity, together with an improvement in serum glucose and lipid metabolic parameters, and with an important improvement in lipid oxidation and a decrease in adipocyte hypertrophy. Moreover, MC-treated animals presented an increased adipose gene expression in EWAT related to lipolysis and fatty acid oxidation. Besides, MC supplementation reduced glucose intolerance and insulin resistance, with an increased expression of the glucose transporter Glut4; and decreases fat accumulation in BAT raising the non-shivering thermogenesis.
Together, this treatment based on a specific combination of metabolic cofactors mitigates important pathophysiological characteristics of obesity, prevailing as a promising clinical treatment against this metabolic disease.
This project is supported by a fellowship from the Vicente Lopez Program (Eurecat) to S. G.-V and by the Catalan government through the funding grant ACCIÓ-Eurecat (PRIV2020-EURHEPAD) to X.E
References:
- Mardinoglu A, Bjornson E, Zhang C, Klevstig M, Söderlund S, Ståhlman M, et al. Personal model‐assisted identification of NAD + and glutathione metabolism as intervention target in NAFLD. Molecular Systems Biology 2017;13:916. https://doi.org/10.15252/msb.20167422.
- Charron MJ, Williams L, Seki Y, Du XQ, Chaurasia B, Saghatelian A, et al. Antioxidant effects of n-acetylcysteine prevent programmed metabolic disease in mice. Diabetes 2020;69:1650–61. https://doi.org/10.2337/db19-1129
- Cantó C, Houtkooper RH, Pirinen E, Youn DY, Oosterveer MH, Cen Y, et al. The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metabolism 2012;15:838–47. https://doi.org/10.1016/j.cmet.2012.04.022.
- Ranjbar Kohan N, Tabandeh MR, Nazifi S, Soleimani Z. L-carnitine improves metabolic disorders and regulates apelin and apelin receptor genes expression in adipose tissue in diabetic rats. Physiol Rep 2020;8. https://doi.org/10.14814/phy2.14641.
Stilbenes from Vitis Vinifera L. wood: study about their stability, interactions, and metabolism related to their biological properties
Biranty Sy 1, Pauline Beaumont 1, Stéphanie Krisa 1, Claude Atgié 2, Tristan Richard 1, Arnaud Courtois 1
1 Unité de Recherche Œnologie, INRAE UMR 1366, Institut des Sciences de la Vigne et du Vin, Université de Bordeaux
2 Chimie Biologie des Membranes et Nano-objets, CNRS, Université de Bordeaux
Stilbenes are non-flavonoid polyphenols found in many plant families. Their most famous and well-studied compounds, resveratrol and one of its dimers, ε-viniferin, are found in relative large amount in the woody part of grapevine1. Numerous literature results highlight their benefits for human health, often in relation to their anti-inflammatory and antioxidant properties that play a central role in many human diseases2. A growing body of evidence indicates that these compounds may exert their biological activities by interacting with each other. As resveratrol and ε-viniferin have been shown to be highly metabolized in the body3,4, there is some interest in studying the biological properties of their metabolites in addition to the potential interactions between these polyphenolic compounds. Thus, the purpose of our work was first to study the interaction of resveratrol and ε-viniferin for their antioxidant and anti-inflammatory activities in an acellular model and a cellular model of rat macrophages (RAW 264.7). Next, we studied the delipidating properties of ε-viniferin and its main glucuronide metabolite in an in vitro model of hepatic steatosis (AML12 cell line).
As resveratrol and ε-viniferin were used in cell models, we first investigated their stability in cell culture medium and showed that they were generally stable with a decline of less than 25% after 48 hours of incubation at 37°C. Moreover, when used in combination, a slowing of degradationwas observed indicating that one compound could stabilize the other. The antioxidant and anti-inflammatory properties of resveratrol and ε-viniferin, alone or in combination, were studied. In a cell-free model, these two stilbenes have the ability to scavenge the NO radical. We have also shown that these molecules exert antioxidant and inflammatory activities in activated macrophages, by inhibiting the production of intracellular reactive oxygen species and NO, an inflammatory marker. The combination of the two molecules showed either synergistic effects in the inhibition of NO production and scavenging, or additive effects in the suppression of intracellular ROS. Given the high glucuronidation of these two stilbenes in vivo, we next undertook experiments on delipidating activities of ε-viniferin-glucuronide (VG). We showed that VG reduces triglyceride accumulation on hepatocytes in an in vitro model of hepatic steatosis, notably by acting on de novo lipogenesis.
This study initially allows us to hypothesize that the use of a plant extract could be beneficial for health insofar as the compounds have a synergistic activity. Secondly, the high metabolism of the compounds does not seem to hinder their biological properties, since the metabolites could themselves be active. The biological properties of resveratrol and ε-viniferin combined, as well as the biological activities of their metabolites, underline the interest of using these natural compounds for the prevention of diseases in which oxidative stress and inflammation are involved.
References:
1. Gabaston J, Leborgne C, Waffo-Teguo P, et al. Wood and roots of major grapevine cultivars and rootstocks: A comparative analysis of stilbenes by UHPLC-DAD-MS/MS and NMR. Phytochem Anal. 2019;30(3):320-331. doi:10.1002/pca.2815
2. Beaumont P, Courtois A, Atgié C, Richard T, Krisa S. In the Shadow of Resveratrol: Biological Activities of Epsilon-Viniferin. https://mib-polyphenol.eu/.
3. Wenzel E, Somoza V. Metabolism and bioavailability of trans-resveratrol. Mol Nutr Food Res. 2005;49(5):472-481. doi:10.1002/mnfr.200500010
4. Beaumont P, Faure C, Courtois A, et al. Trans-ε-Viniferin Encapsulation in Multi-Lamellar Liposomes: Consequences on Pharmacokinetic Parameters, Biodistribution and Glucuronide Formation in Rats. 2021. doi:10.3390/nu13124212
Dietary pattern focused on macro and micronutrients intake and its association with body mass and waist circumference index in patients with prodromal Alzheimer's disease in La Rioja
Silvia Yuste 1, Patricia Pérez-Matute 2, Sara López Alava 3, Belinda Matute Tobías 3, Cristina Lozano-Ochoa 4, Emma Recio-Fernández 2, María Eugenia Marzo Sola 3, María Íñiguez 2, María-José Motilva 1
1 Spanish National Research Council (CSIC). Institute of Grapevine and Wine Sciences (ICVV), Logroño, Spain.
2 Infectious Diseases, Microbiota and Metabolism Unit. CIBIR- Hospital Universitario San Pedro, Logroño, Spain.
3 Neurology Section. Hospital Universitario San Pedro, Logroño, Spain.
4 Predepartmental Nursing Unit. University of La Rioja, Logroño, Spain
Functional decline (dementia) during aging results in the deterioration of physical and cognitive capacities. The most common form of dementia is Alzheimer's disease that accounts for 60% of all patients with dementia. Unfortunately, there are no effective or preventive treatments for this disease [1]. Addressing modifiable risk factors is considered to be the most promising strategy to prevent or delay Alzheimer's disease. In this regard, diet is a modifiable environmental factor that has been associated with many non-communicable diseases with connections to dementia [2]. A large body of scientific evidence, mostly observational studies, suggests a direct role for dietetic habits nutrition on clinical measures of cognitive status in older adults. Due to the complex biological interactions between different components of the diet, it has been proposed that the use of a whole-diet approach, through the study of dietary patterns rather than individual nutrients or food groups, might help to understand the role of diet in Alzheimer’s disease and related dementia [3]. Thus, the aim of the study was to establish the connections between dietetic habits, body mass and waist index in the protection against Alzheimer's disease in an environment of other multiple lifestyle factors. To achieve this goal, a retrospective observational study of cases and controls has been carried out. For this, 95 volunteers have been studied: 46 were included in the Alzheimer group (mean age 70.4) and 49 in the control group (mean age 65.0). For the diet and nutritional evaluation, the Food Frequency Questionnaire (FFQ) and the Three-Day Record (3-DR) were used. FFQ includes 115 foods structured in 9 groups [4] and, based on these data, the level of adherence to the Mediterranean Diet was also calculated. In addition, the 3-DR is a prospective method in an open format which collects information on the foods and beverages consumed in a previously specified period of time [5]. From this, the analysis of the average daily intake of energy, macro- and micronutrients was carried out using the PCN Pro food composition database [6]. The results showed that the controls have a statistically higher body mass index (BMI) than the Alzheimer cases (27.6 vs 25.7 p=0.0137). No statistically significant differences were observed with respect to the waist index. In the analysis of the dietary pattern, the levels of adherence to the Mediterranean Diet suggests a slightly higher adherence in the control group (score 9.24/14) compared to the Alzheimer’s disease group (score 8.83/14), although this difference was not statistically significant. The analysis of macro and micronutrients showed that the control participants daily ingested higher amounts of polyunsaturated fatty acids (p=0.032), iron (p=0.040), folic acid (p=0.009), vitamin C (p=0.030) and vegetal proteins (p=0.021). In contrast, patients with Alzheimer's disease daily ingested statistically higher amounts of phosphorus (p=0.025) and animal proteins (p=0.025). The dietary data contrast with the BMI and waist index observed in the two groups. More studies are needed to understand such lack of associations among dietary intake and BMI in our cohort.
This study was supported by Ministerio de Ciencia, Innovación y Universidades (MCIN/AEI/10.13039/5011000 11033) (Spanish Goverment) throught the project PID2019-108851RB-C22 and the Margarita Salas postdoctoral grant (funded by the European Union – NextGenerationEU).
References:
1. Breijyeh, Z.; Karaman, R. Comprehensive review on Alzheimer’s disease: causes and treatment. Molecules. 2020; 25(24), 5789. doi: 10.3390/molecules25245789
2. Agarwal, S. K. Diet and Non-Communicable Diseases: Part II Cancer, Diabetes Mellitus, Kidney Diseases, Alzheimer’s Disease, Arthritis. Clinical Medicine Insights. 2021; 2(4), 224-243. doi: 10.52845/CMI/2021-2-4-2
3. Scarmeas, N.; Anastasiou, C. A.; Yannakoulia, M. Nutrition and prevention of cognitive impairment. The Lancet Neurology. 2018; 17(11), 1006-1015. doi: 10.1016/S1474-4422(18)30338-7
4. Trinidad Rodríguez, I.; Fernández Ballart, J.; Cucó Pastor, G.; Biarnés Jordà, E.; Arija Val, V. Validación de un cuestionario de frecuencia de consumo alimentario corto: Reproducibilidad y validez. Nutricion Hospitalaria. 2008; 23(3), 242–252
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5. Ortega, R. M.; Perez-Rodrigo, C.; Lopez-Sobaler, A. M. Dietary assessment methods: Dietary records [Métodos de evaluación de la ingesta actual: Registro o diario dietético]. Nutricion Hospitalaria. 2015; 31, 38–45. doi: 10.14642/RENC.2015.21.sup1.5048
6. Cantós López, D.; Farran, A.; Palma Linares, I. Programa de Càlcul Nutricional Professional (PCN Pro). 2013. http://hdl.handle.net/2445/44329
... some of the attendants are taking a refreshment in the patio of the Jaca University Building
... while other have a look at the book of the abstracts of the meeting
... while other have a look at the book of the abstracts of the meeting