Involvement of autophagy in the beneficial effects of resveratrol in hepatic steatosis treatment. A comparison with energy restriction

Autophagy eliminates damaged cellular components. In the liver, it has been proposed that it mediates the breakdown of lipid droplets. This study aimed to compare the involvement of autophagy and the oxidative status in the effects of resveratrol and energy restriction as therapeutic tools for managing liver steatosis. In addition, potential additive or synergic effects were studied. Rats were fed a high-fat high-sucrose diet for 6 weeks and then divided into four experimental groups and fed a standard diet: a control group (C), a resveratrol-treated group (RSV, 30 mg kg−1 d−1), an energy restricted group (R, −15%), and an energy restricted group treated with resveratrol (RR). Liver triacylglycerols (TGs) were measured by Folch's method. TBARS, GSH, GSSG, GPx and SOD were assessed using commercial kits. The protein expression of beclin, atg5 and p62, as well as ratios of pSer555 ULK1/total ULK1, pSer757 ULK1/total ULK1 and LC3 II/I were determined by western blotting. Energy restriction increased the protein expression of beclin, atg5 and pSer757 ULK1/total ULK1 and LC3 II/I ratios, and reduced the protein expression of p62, thus indicating that it induced autophagy activation. The effects of resveratrol were similar but less marked than the hypocaloric diet. No differences were observed in oxidative stress determinants except for TBARS, which was decreased by energy restriction. In conclusion, resveratrol can reverse partially dietary-induced hepatic lipid accumulation, although less efficiently than energy restriction. The delipidating effect of energy restriction is mediated in part by the activation of autophagy; however, the involvement of this process in the effects of resveratrol is less clear

Do the Effects of Resveratrol on Thermogenic and Oxidative Capacities in IBAT and Skeletal Muscle Depend on Feeding Conditions?

The aim of this study was to compare the effects of mild energy restriction and resveratrol on thermogenic and oxidative capacity in interscapular brown adipose tissue (IBAT) and in skeletal muscle. Rats were fed a high-fat high-sucrose diet for six weeks, and divided into four experimental groups fed a standard diet: a control group, a resveratrol-treated group, an energy-restricted group and an energy-restricted group treated with resveratrol. Weights of IBAT, gastrocnemius muscle and fat depots were measured. Activities of carnitine palmitoyltransferase (CPT) and citrate synthase (CS), protein levels of sirtuin (SIRT1 and 3), uncoupling proteins (UCP1 and 3), glucose transporter (GLUT4), mitochondrial transcription factor (TFAM), nuclear respiratory factor (NRF1), peroxisome proliferator-activated receptor (PPAR) and AMP activated protein kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator (PGC1) activation were measured. No changes in IBAT and gastrocnemius weights were found. Energy-restriction, but not resveratrol, decreased the weights of adipose depots. In IBAT, resveratrol enhanced thermogenesis activating the SIRT1/PGC1/PPAR axis. Resveratrol also induced fatty acid oxidation and glucose uptake. These effects were similar when resveratrol was combined with energy restriction. In the case of gastrocnemius muscle, the effects were not as clear as in the case of IBAT. In this tissue, resveratrol increased oxidative capacity. The combination of resveratrol and energy restriction seemingly did not improve the effects induced by the polyphenol alone.This research was funded by MINECO (AGL-2015-65719-R-MINECO/FEDER, UE), University of the Basque Country (ELDUNANOTEK UFI11/32), Instituto de Salud Carlos III (CIBERobn) and Basque Government (IT-572-13). Inaki Milton-Laskibar is a recipient of a doctoral fellowship from the Gobierno Vasco

Antidiabetic effects of natural plant extracts via inhibition of carbohydrate hydrolysis enzymes with emphasis on pancreatic alpha amylase

Introduction: The increasing prevalence of type 2 diabetes mellitus and the negative clinical outcomes observed with the commercially available anti-diabetic drugs have led to the investigation of new therapeutic approaches focused on controlling postprandrial glucose levels. The use of carbohydrate digestive enzyme inhibitors from natural resources could be a possible strategy to block dietary carbohydrate absorption with less adverse effects than synthetic drugs. Areas covered: This review covers the latest evidence regarding in vitro and in vivo studies in relation to pancreatic alpha-amylase inhibitors of plant origin, and presents bioactive compounds of phenolic nature that exhibit anti-amylase activity. Expert opinion: Pancreatic alpha-amylase inhibitors from traditional plant extracts are a promising tool for diabetes treatment. Many studies have confirmed the alpha-amylase inhibitory activity of plants and their bioactive compounds in vitro, but few studies corroborate these findings in rodents and very few in humans. Thus, despite some encouraging results, more research is required for developing a valuable anti-diabetic therapy using pancreatic alpha-amylase inhibitors of plant origin

Correlation between serum advanced glycation end products and dietary intake of advanced glycation end products estimated from home cooking and food frequency questionnaires

Abstract Background & aims: To our knowledge the association between dietary advanced glycation end-products (dAGEs) and cardiometabolic disease is limited. Our aim was to examine the association between dAGEs and serum concentration of carboxymethyl-lysine (CML) or soluble receptor advanced glycation end-products (sRAGEs), and to assess the difference on dAGEs and circulating AGEs according to lifestyle and biochemical measures. Methods and results: 52 overweight or obese adults diagnosed with type 2 diabetes were included in this cross-sectional analysis. dAGEs were estimated from a Food Frequency Questionnaire (FFQ) or from a FFQ þ Home Cooking Frequency Questionnaire (HCFQ). Serum concentrations of CML and sRAGEs were measured by ELISA. Correlation tests were used to analyze the association between dAGEs derived from the FFQ or FFQ þ HCFQ and concentrations of CML or sRAGEs. Demographic characteristics, lifestyle factors and biochemical measures were analyzed according to sRAGEs and dAGEs using student t-test and ANCOVA. A significant inverse association was found between serum sRAGEs and dAGEs estimated using the FFQ þ HCFQ (r Z 0.36, p Z 0.010), whereas no association was found for dAGEs derived from the FFQ alone. No association was observed between CML and dAGEs. dAGEs intake estimated from the FFQ þ HCFQ was significantly higher among younger and male participants, and in those with higher BMI, higher Hb1Ac levels, longer time with type 2 diabetes, lower adherence to Mediterranean diet, and higher use of culinary techniques that generate more AGEs (all p values p < 0.05). Conclusions: These results show knowledge on culinary techniques is relevant to derive the association between dAGEs intake and cardiometabolic risk factors

Impact of polyphenols and polyphenol-rich dietary sources on gut microbiota composition

Gut microbiota plays a key role in host physiology and metabolism. Indeed, the relevance of a well-balanced gut microbiota composition to an individual´s health status is essential for the person's well-being. Currently, investigations are focused on analyzing the effects of pre- and probiotics as new therapeutic tools to counteract the disruption of intestinal bacterial balance occurring in several diseases. Polyphenols exert a wide range of beneficial health effects. However, although specific attention has been paid in recent years to the function of this “biological entity” in the metabolism of polyphenols, less is known about the modulatory capacity of these bioactive compounds on gut microbiota composition. This review provides an overview of the latest investigations carried out with pure polyphenols, extracts rich in polyphenols and polyphenol-rich dietary sources (such as cocoa, tea, wine, soy products and fruits), and critically discusses the consequences to gut microbiota composition which are produced

Shifts in microbiota species and fermentation products in a dietary model enriched in fat and sucrose

The gastrointestinal tract harbours a “superorganism” called the gut microbiota, which is known to play a crucial role in the onset and development of diverse diseases. This internal ecosystem, far from being a static environment, could be willingly manipulated by diet and dietary components. Feeding animals with high-fat sucrose diets entails diet-induced obesity, a model which is usually used in research to mimic the obese phenotype of Western societies. The aim of the present study was to identify gut microbiota dysbiosis and associated metabolic changes produced in 5 male Wistar rats fed a high-fat sucrose (HFS) diet for six weeks and to compare it with the basal microbial composition. For this purpose, DNA extracted from faeces at baseline and after the treatment was analysed by amplification of the V4-V6 region of the 16S ribosomal DNA (rDNA) gene using 454 pyrosequencing. Short-chain fatty acids (SCFA), acetate, propionate and butyrate, were also evaluated by gas chromatography-mass spectrometry (GC-MS). At the end of the treatment, gut microbiota composition significantly differed at phylum level (Firmicutes, Bacteroidetes and Proteobacteria) and class level (Erisypelotrichi, Deltaproteobacteria, Bacteroidia and Bacilli). Interestingly, Clostridia class showed a significant decrease after the HFS-diet treatment, which correlated with visceral adipose tissue, and is likely mediated by dietary carbohydrates. Of particular interest, Clostridium cluster XIVa species were significantly reduced and changes were identified in the relative abundance of other specific bacterial species (Mitsuokella jalaludinii, Eubacterium ventriosum, Clostridium sp. FCB90-3, Prevotella nanceiensis, Clostridium fusiformis, Clostridium sp. BNL1100 and Eubacterium cylindroides) that, in some cases, showed opposite trends to their relative families. These results highlight the relevance of characterizing gut microbial population differences at species level and contribute to understand the plausible link between the 1 diet and specific gut bacterial species that are able to influence the inflammatory status, intestinal barrier function and obesity development. Keywords: gut microbiota, pyrosequencing, high-fat sucrose diet, short chain fatty acids, Erysipelotrich

Reshaping faecal gut microbiota composition by the intake of trans-resveratrol and quercetin in high-fat sucrose diet-fed rats

Diet‐induced obesity is associated to an imbalance in the normal gut microbiota composition. Resveratrol and quercetin, widely known for their health beneficial properties, have low bioavailability and, when reach the colon, they are targets of the gut microbial ecosystem. Hence, the use of these molecules in obesity might be considered as a potential strategy to modulate intestinal bacterial composition. The purpose of this study was to determine whether trans‐resveratrol and quercetin administration could counteract gut microbiota dysbiosis produced by high‐fat sucrose diet (HFS) and in turn, improve gut health. Wistar rats were randomized into four groups fed a HFS diet supplemented or not with trans‐resveratrol (15 mg/kg BW/day), quercetin (30 mg/kg BW/day) or a combination of both polyphenols at those doses. Administration of both polyphenols together prevented body‐weight gain and reduced serum insulin levels. Moreover, individual supplementation of trans‐resveratrol and quercetin effectively reduced serum insulin levels and insulin resistance. Quercetin supplementation generated a great impact on gut microbiota composition at different taxonomic levels, attenuating Firmicutes/Bacteroidetes ratio and inhibiting the growth of bacterial species previously associated to diet‐induced obesity (Erysipelotrichaceae, Bacillus, Eubacterium 1 cylindroides). Overall, the administration of quercetin was found to be effective in lessening HFS diet‐induced gut microbiota dysbiosis. In contrast, trans‐resveratrol supplementation alone or in combination with quercetin, scarcely modified the profile of gut bacteria, but acted at intestinal level altering the mRNA expression of tight‐junction proteins (TJPs) and inflammation associated genes

Metabolic faecal fingerprinting of trans-resveratrol and quercetin following a high-fat sucrose dietary model using liquid chromatography coupled to high-resolution mass spectrometry

Faecal non‐targeted metabolomics deciphers metabolic end‐products resulting from the interactions among food, host genetics, and gut microbiota. Faeces from Wistar rats fed a high‐fat sucrose (HFS) diet supplemented with trans‐resveratrol and quercetin (separately or combined) were analysed by liquid chromatography coupled to high‐resolution mass spectrometry (LC‐HRMS). Metabolomics in faeces are categorised into four clusters based on the type of treatment. Tentative identification of significantly differing metabolites highlighted the presence of carbohydrate derivatives or conjugates (3‐phenylpropyl glucosinolate and dTDP‐D‐mycaminose) in quercetin group. The trans‐resveratrol group was differentiated by compounds related to nucleotides (uridine monophosphate and 2,4‐dioxotetrahydropyrimidine D‐ribonucleotide). Marked associations between bacterial species (Clostridium genus) and the amount of some metabolites were identified. Moreover, trans‐resveratrol and resveratrol‐derived microbial metabolites (dihydroresveratrol and lunularin) were also identified. Accordingly, this study confirms the usefulness of omics‐based techniques to discriminate individuals depending on the physiological effect of food constituents and represents an interesting tool to assess the impact of future personalized therapies