Metabolic Impact of Flavonoids Consumption in Obesity: From Central to Peripheral

The prevention and treatment of obesity is primary based on the follow-up of a healthy lifestyle, which includes a healthy diet with an important presence of bioactive compounds such as polyphenols. For many years, the health benefits of polyphenols have been attributed to their anti-oxidant capacity as free radical scavengers. More recently it has been described that polyphenols activate other cell-signaling pathways that are not related to ROS production but rather involved in metabolic regulation. In this review, we have summarized the current knowledge in this field by focusing on the metabolic e ects of flavonoids. Flavonoids are widely distributed in the plant kingdom where they are used for growing and defensing. They are structurally characterized by two benzene rings and a heterocyclic pyrone ring and based on the oxidation and saturation status of the heterocyclic ring flavonoids are grouped in seven di erent subclasses. The present work is focused on describing the molecular mechanisms underlying the metabolic impact of flavonoids in obesity and obesity-related diseases. We described the e ects of each group of flavonoids in liver, white and brown adipose tissue and central nervous system and the metabolic and signaling pathways involved on them

Lyophilized Maqui (Aristotelia chilensis) Berry Induces Browning in the Subcutaneous White Adipose Tissue and Ameliorates the Insulin Resistance in High Fat Diet-Induced Obese Mice

Maqui (Aristotelia Chilensis) berry features a unique profile of anthocyanidins that includes high amounts of delphinidin-3-O-sambubioside-5-O-glucoside and delphinidin-3-O-sambubioside and has shown positive effects on fasting glucose and insulin levels in humans and murine models of type 2 diabetes and obesity. The molecular mechanisms underlying the impact of maqui on the onset and development of the obese phenotype and insulin resistance was investigated in high fat diet-induced obese mice supplemented with a lyophilized maqui berry. Maqui-dietary supplemented animals showed better insulin response and decreased weight gain but also a differential expression of genes involved in de novo lipogenesis, fatty acid oxidation, multilocular lipid droplet formation and thermogenesis in subcutaneous white adipose tissue (scWAT). These changes correlated with an increased expression of the carbohydrate response element binding protein b (Chrebpb), the sterol regulatory binding protein 1c (Srebp1c) and Cellular repressor of adenovirus early region 1A-stimulated genes 1 (Creg1) and an improvement in the fibroblast growth factor 21 (FGF21) signaling. Our evidence suggests that maqui dietary supplementation activates the induction of fuel storage and thermogenesis characteristic of a brown-like phenotype in scWAT and counteracts the unhealthy metabolic impact of an HFD. This induction constitutes a putative strategy to prevent/treat diet-induced obesity and its associated comorbidities

Effects and underlying mechanisms of bioactive compounds-enriched diets against obesity and associated pathologies

[eng] Bioactive compounds have long been proposed as a tool to help facing both obesity and its comorbidities pandemic. Knowledge on their properties, together with the discovery of new therapeutic targets in animals and humans, make then interesting proposals for the prevention and treatment of various metabolic diseases. One of the main parts of this thesis proposal was to evaluate the ability of a pure, isolated polyphenol supplementation to counteract the pernicious metabolic effects of a high-fat diet on a murine model. Contrary to expectations, the polyphenolic supplementation worsened the action of the high-fat diet and pointedly produced an aggression to the kidneys. The other main part of this thesis proposal had been to assess a natural source of bioactive compounds with a broad and diverse profile not only in phenolic species, on a diet-obesity model. Based on the experience of our research group and the positive results demonstrated in different studies on chronic diseases, the Rosa canina fruit was chosen. In this case it was demonstrated how the supplementation with Rosa canina flesh was able to slow down the pernicious effect of the high fat diet, and particularly how exhibited a strong anti-steatotic effect on liver by downregulating several key genes, and thus improving significantly the non-alcoholic fatty liver disease course on obese mice. Furthermore, through the flesh fractionation, bioactive compound characterization and in vitro analysis, it was possible to identify that the most lipophilic phases of the Rosa canina show an antagonistic role on the peroxisome proliferator activated receptor gamma and therefore were partly responsible for the observed anti-steatotic effect.[cat] Els compostos bioactius han estat proposats com a eina dietètica per a fer front a la pandèmica de l’obesitat i de les seves comorbiditats. El coneixement de les seves propietats, junt amb la cerca de noves dianes terapèutiques en animals i humans, els converteixen en una proposta interessant per a la prevenció i el tractament de diverses malalties metabòliques. Una de les principals parts d'aquesta proposta de tesi doctoral ha sigut avaluar la capacitat d'una suplementació de polifenols aïllats purs vers els efectes perniciosos d'una dieta d'alt contingut en greix en el metabolisme sobre un model murí. En contra a les expectatives, la suplementació amb la mescla de polifenols va empitjorar notòriament l’acció de la dieta alta en greix i va produir una clara agressió als ronyons. L’altra part principal d’aquesta proposta de tesi doctoral ha sigut avaluar una font natural de compostos bioactius però amb un ampli i divers perfil d’espècies. Basant-nos en l’experiència del nostre grup de recerca i en resultats previs positius demostrats en diversos estudis sobre malalties cròniques, es va triar el fruit de la Rosa canina. En aquest cas, es va demostrar com la suplementació amb la polpa de Rosa canina va ser capaç de frenar l'efecte perniciós de la dieta d'alt greix, i en particular com va exhibir un fort efecte antiestatotic sobre el fetge mitjançant la regulació de diversos gens clau, i així millorant significativament el quadre de l’esteatosi hepàtica no alcohòlica. Paral·lelament, mitjançant el fraccionament de la polpa, la caracterització dels compostos bioactius i l'anàlisi in vitro, va ser possible identificar que les fases més lipòfiles de la Rosa canina exercien un paper antagonista del receptor PPAR-gamma i que per tant, eren en part responsables de l'efecte antiestatotic observat

A Mixture of Pure, Isolated Polyphenols Worsens the Insulin Resistance and Induces Kidney and Liver Fibrosis Markers in DietInduced Obese Mice

t: Obesity is a worldwide epidemic with severe metabolic consequences. Polyphenols are secondary metabolites in plants and the most abundant dietary antioxidants, which possess a wide range of health effects. The most relevant food sources are fruit and vegetables, red wine, black and green tea, coffee, virgin olive oil, and chocolate, as well as nuts, seeds, herbs, and spices. The aim of this work was to evaluate the ability of a pure, isolated polyphenol supplementation to counteract the pernicious metabolic effects of a high-fat diet (HFD). Our results indicated that the administration of pure, isolated polyphenols under HFD conditions for 26 weeks worsened the glucose metabolism in diet-induced obese mice. The data showed that the main target organ for these undesirable effects were the kidneys, where we observed fibrotic, oxidative, and kidney-disease markers. This work led us to conclude that the administration of pure polyphenols as a food supplement would not be advisable. Instead, the ingestion of complete "whole" foods would be the best way to get the health effects of bioactive compounds such as polyphenols