Lactobacillus rhamnosus GG administration partially prevents diet-induced insulin resistance in rats: a comparison with its heat-inactivated parabiotic.

Insulin resistance and type 2 diabetes are obesity-related health alterations, featuring an ever-increasing prevalence. Besides inadequate feeding patterns, gut microbiota alterations stand out as potential contributors to these metabolic disturbances. The aim of this study was to investigate whether the administration of a probiotic (Lactobacillus rhamnosus GG) effectively prevents diet-induced insulin resistance in rats and to compare these potential effects with those exerted by its heat-inactivated parabiotic. For this purpose, 34 male Wistar rats were fed a standard or a high-fat high-fructose diet, alone or supplemented with viable or heat-inactivated Lactobacillus rhamnosus GG. The body and white adipose tissue weight increases, induced by the obesogenic diet, were prevented by probiotic and parabiotic administration. The trend towards higher basal glucose levels and significantly higher serum insulin concentration observed in the non-treated animals fed with the obesogenic diet were effectively reverted by both treatments. Similar results were also found for serum adiponectin and leptin, whose levels were brought back by the probiotic and parabiotic administration to values similar to those of the control animals. Noteworthily, parabiotic administration significantly reduced skeletal muscle triglyceride content and activated CPT-1b compared to the non-treated animals. Finally, both treatments enhanced Akt and AS160 phosphorylation in the skeletal muscle compared to the non-treated animals; however, only parabiotic administration increased GLUT-4 protein expression in this tissue. These results suggest that heat-inactivated Lactobacillus rhamnosus GG seem to be more effective than its probiotic of origin in preventing high-fat high-fructose diet-induced insulin resistance in rats.

Role of chemerin in the control of glucose homeostasis.

Chemerin is an adipokine produced by the white adipose tissue and other tissues, which plays various roles in the pathogenesis of inflammatory and metabolic diseases in multiple organs. The present review aims at gathering scientific evidence reported in the last ten years, concerning the relationship of chemerin with alterations of glycaemic control, such as insulin resistance, type 2 diabetes and gestational diabetes in humans. Although the vast majority of the studies have shown a positive correlation between the chemerin level and a bad glycaemic control, a general consensus has not been reached. The reported results come from case-control and observational longitudinal studies, thereby limiting their interpretation. In fact, it cannot be stated whether insulin resistance and diabetes lead to an increase in chemerin levels or, on the contrary, if high levels of chemerin contribute to an impaired glycaemic control. Elevated levels of circulating chemerin are also associated with gestational diabetes mellitus. Chemerin gene polymorphisms could be proposed as mediators of glucose-related diseases. Nevertheless, to date very little is known about their implication in glucose metabolism. With regard to the mechanisms of action, chemerin impairs insulin cascade signaling by acting on several proteins of this cascade and by inducing inflammation.

Pterostilbene modifies triglyceride metabolism in hepatic steatosis induced by high-fat high-fructose feeding: a comparison with its analog resveratrol.

The use of phenolic compounds as a new therapeutic approach against NAFLD has emerged recently. In the present study, we aim to study the effect of pterostilbene in the prevention of liver steatosis developed as a consequence of high-fat (saturated) high-fructose feeding, by analysing the changes induced in metabolic pathways involved in triglyceride accumulation. Interestingly, a comparison with the anti-steatotic effect of its parent compound resveratrol will be made for the first time. Rats were distributed into 5 experimental groups and fed either a standard laboratory diet or a high-fat high-fructose diet supplemented with or without pterostilbene (15 or 30 mg per kg per d) or resveratrol (30 mg per kg per d) for 8 weeks. Serum triglyceride, cholesterol, NEFA and transaminase levels were quantified. Liver histological analysis was carried out by haematoxylin-eosin staining. Different pathways involved in liver triglyceride metabolism, including fatty acid synthesis, uptake and oxidation, triglyceride assembly and triglyceride release, were studied. Pterostilbene was shown to partially prevent high-fat high-fructose feeding induced liver steatosis in rats, demonstrating a dose-response pattern. In this dietary model, it acts mainly by reducing de novo lipogenesis and increasing triglyceride assembly and release. Improvement in mitochondrial functionality was also appreciated. At the same dose, the magnitude of pterostilbene and resveratrol induced effects, as well as the involved mechanisms of action, were similar.

The influence of dietary conditions in the effects of resveratrol on hepatic steatosis.

Non-alcoholic fatty liver disease (NAFLD) is considered the major cause for the development of chronic liver alterations. Hepatic steatosis is the most benign and common form of NAFLD, although its potential to evolve into more detrimental liver alterations makes its treatment necessary. In this regard, much attention has been paid to polyphenols, with resveratrol being one of the most studied ones. This review is aimed at studying the effects induced by resveratrol on hepatic steatosis in both preclinical studies conducted under different feeding conditions (overfeeding, normal feeding and caloric restriction), and in clinical trials. The vast majority of studies have been conducted by administering the polyphenol at the same time as an obesogenic diet. Under these experimental conditions, resveratrol has shown effectiveness improving diet-induced excessive liver lipid accumulation. Data are scarce for studies carried out by administering resveratrol under standard or energy-restricted feeding conditions. In this regard, while resveratrol retains its effectiveness, ameliorating hepatic steatosis under standard feeding conditions, such an effect has not been reported for the administration of the polyphenol under energy restriction. With regard to clinical trials, in the majority of them, resveratrol did not show its effectiveness in improving hepatic steatosis. This lack of effect could be due to significant differences in the experimental procedures (mainly the length of the experimental period). The relevance of liver fat content at the baseline should also be considered. Altogether, there is no sufficient scientific support so far for proposing resveratrol as a tool for hepatic steatosis treatment.

Effects of resveratrol and its derivative pterostilbene on brown adipose tissue thermogenic activation and on white adipose tissue browning process.

The main function of brown adipose tissue (BAT) is thermogenesis, a process mediated by uncoupling protein 1 (UCP1), which is located in the inner mitochondrial membrane and acts uncoupling oxidative phosphorylation from ATP production, thereby dissipating energy as heat. White adipose tissue can also express UCP1 positive cells due to a process known as browning. This phenomenon could also increase the thermogenic effect in the classical brown adipose depots. BAT thermogenesis depends, among other factors on both, nutritional conditions and food availability. Indeed, some studies have found that BAT recruitment and function are enhanced by some food components. The present study focuses on the effects of resveratrol and pterostilbene, two phenolic compounds belonging to the stilbene group, on BAT thermogenic activation and white adipose tissue browning process. The reported studies, carried out in cell cultures and animal models, show that both resveratrol and pterostilbene induce thermogenic capacity in interscapular BAT by increasing mitochondriogenesis, as well as enhancing fatty acid oxidation and glucose disposal. In addition, resveratrol seems to promote browning by activating peroxisome proliferator-activated receptor (PPAR), while the lack of changes in mitochondrial biogenesis suggests that probably the browning process occurs by direct resveratrol-mediated upregulation of ucp1 mRNA expression.

Has the adipokine profile an influence on the catch-up growth type in small for gestational age infants?

Infants born small for gestational age (SGA) are at increased risk of perinatal morbidity, persistent short stature, and metabolic alterations in later life. Moreover, the post-natal growth pattern of SGA infants may be an important contributor to health outcomes later in life, which can be influenced by adipokines. The aims of this study were to compare plasma adipokine profiles (leptin, adiponectin, vaspin, chemerin, and nephroblastoma overexpressed (NOV/CCN3)) among SGA newborns aged 3 months, with low, normal, or high catch-up, to search for potential differences between males and females and to analyze the evolution of several adipokines in plasma from SGA newborns between 3 and 24 months. This prospective, longitudinal study was addressed in SGA Caucasian subjects at Hospital Universitario de Álava-Txagorritxu. We observed that infants with fast catch-up showed significantly lower birth weight than the other two groups. As far as adipokines are concerned, they could have an influence on catch-up type because differences among the three experimental groups were found. It may be proposed that health prognoses in infants with slow and fast catch-up are opposite, not only in adulthood but also during their first months. Finally, adipokine evolution patterns during the first 24 months of age differ, depending on the adipokine, and 24-month-old males show lower levels of leptin, adiponectin, and omentin than females.

Effects of resveratrol and its analogue pterostilbene, on NOV/CCN3 adipokine in adipose tissue from rats fed a high-fat high-sucrose diet.

Nephroblastoma overexpressed protein, also called NOV/CCN3, is an adipokine which is present in various tissues and recently linked to obesity. The objective of the study was to determine the effect of resveratrol and pterostilbene on NOV/CCN3 in adipose tissue from rats fed an obesogenic diet. Thirty-six male Wistar rats were split into four groups (n = 9): fed a standard diet (CC), high-fat high-sucrose (HFS) diet supplemented with resveratrol (RSV; 30 mg/kg/day) or with pterostilbene (PT; 30 mg/kg/day), or without phenolic supplementation (HFS). Rats were sacrificed after 6 weeks of treatment, and adipose tissue (white and brown) from different anatomical locations were dissected. Then, Nov/ccn3 gene and protein expression and the adipogenic genes, Ucp-1 and Pgc-1a, expressions were studied. Increased weight of white adipose tissues was found in rats fed the HFS diet. Whereas resveratrol-treated rats showed reduced internal and total adipose tissue weights, pterostilbene-treated rats showed reduced subcutaneous, internal and total adipose depots. Nov/ccn3 gene expression decreased in epididymal and interscapular brown depot in rats fed HFS diet when compared with the control group. Regarding the phenolic compounds, resveratrol prompted a Nov/ccn3 gene expression increase in epididymal fat tissue, whereas pterostilbene reduced its protein expression compared with the obese group. However, these phenolic compounds did not affect NOV/CCN3 expression in brown depot. NOV/CCN3 seems to be involved in weight changes in epididymal adipose tissue under obesogenic feeding, but not in subcutaneous, acting as a protective mechanism counteracting the fattening effect of the diet. To our knowledge, this is the first study analyzing whether NOV/CCN3 is involved in the anti-obesity effect of resveratrol and pterostilbene. Our results suggest that this is not the case.

A randomised controlled trial of a program based on the theory of planned behavior to promote fruit and vegetable intake among schoolchildren: PROFRUVE study protocol.

BACKGROUND: The PROFRUVE study is a controlled intervention based on the Theory of Planned Behavior (TPB), which follows those behavioral theories that have proved to be the most effective at changing infant fruit and vegetable (FV) intake pattern. The main purpose of the study is to evaluate the effectiveness of an intervention program in increasing FV consumption in schoolchildren aged 8 to 10 and based on TPB. METHODS: Eligible classrooms within schools from Vitoria-Gasteiz (Basque Country, Spain) will be randomly assigned to the intervention (classrooms n = 4; children n = 86) or control (classrooms n = 4; children n = 86) group. The intervention group will receive 14 sessions of 60 min during an academic year (October to June). These sessions, designed by a multidisciplinary team, are based on TPB and are directed at modifying determinants of behavior (attitudes, subjective norms, perceived behavioral control and intention of consumption), and intake of FV itself. Both the process and the evolution of consumption and determinants of behavior will be evaluated (before, during, shortly after and a year after) using validated surveys, 7 day food records, 24 h reminders and questionnaires. DISCUSSION: This study will provide a valid and useful tool to achieve changes in the consumption of FV at school level. A negative result will be helpful in redefining new strategies in the framework of changing habits in the consumption of FV. TRIAL REGISTRATION: This study has been retrospectively registered at ClinicalTrials.gov. Identifier: NCT03400891 . Data registered: 17/01/2018.

Olive oil in the prevention and management of type 2 diabetes mellitus: a systematic review and meta-analysis of cohort studies and intervention trials.

BACKGROUND/OBJECTIVES: Olive oil (OO) as food is composed mainly of fatty acids and bioactive compounds depending from the extraction method. Both had been discussed as health promoting with still open questions. Thus, we conducted a meta-analysis to illustrate the impact of this food on type 2 diabetes (T2D) by investigating the association between OO intake and risk of T2D, and the effect of OO intake in the management of T2D. SUBJECTS/METHODS: Searches were performed in PubMed, Cochrane Library and google scholar. First, we conducted a random effect meta-analysis of prospective cohort studies and trials investigating the association between OO and risk of T2D. Second, a meta-analysis was performed to detect the effects of olive oil on glycemic control in patients with T2D. RESULTS: Four cohort studies including 15 784 T2D cases and 29 trials were included in the meta-analysis. The highest OO intake category showed a 16% reduced risk of T2D (RR: 0.84; 95% CI: 0.77, 0.92) compared with the lowest. However, we observed evidence for a nonlinear relationship. In T2D patients OO supplementation resulted in a significantly more pronounced reduction in HbA1c (MD: -0.27%; 95% CI: -0.37, -0.17) and fasting plasma glucose (MD: -0.44 mmol l-1; 95% CI -0.66, -0.22) as compared with the control groups. CONCLUSIONS: This meta-analysis provides evidence that the intake of OO could be beneficial for the prevention and management of T2D. This conclusion regards OO as food, and might not been valid for single components comprising this food.

Comparative effects of energy restriction and resveratrol intake on glycemic control improvement.

Resveratrol (RSV) has been proposed as an energy restriction mimetic. This study aimed to compare the effects of RSV and energy restriction on insulin resistance induced by an obesogenic diet. Any additive effect of both treatments was also analyzed. Rats were fed a high-fat high-sucrose diet for 6 weeks. They were then distributed in four experimental groups which were either fed a standard control diet (C), or treated with RSV (30 mg/kg/d), or submitted to energy restriction (R, 15%), or treated with RSV and submitted to energy restriction (RR). A glucose tolerance test was performed, and serum glucose, insulin, fructosamine, adiponectin, and leptin concentrations determined. Muscle triacylglycerol content and protein expression of insulin receptor (IRß), protein kinase B (Akt), Akt substrate of 160 kDa (AS160) and glucose transporter 4 (GLUT-4) were measured. In RSV rats, fructosamine concentrations were reduced, HOMA-IR remained unchanged, but glucose tolerance was improved, without changes in phosphorylation of IRß, Akt, and AS160 or in GLUT-4 protein expression. Rats under energy restriction showed an improvement in all the markers related to glycemic control, as well as increased phosphorylation of AS160 and protein expression of GLUT-4. In rats from RR group the results were similar to R group, with the exception of IRß and Akt phosphorylation, which were increased. In conclusion, mild energy restriction is more efficient than intake of RSV within a standard balanced diet, and acts by means of a different mechanism from that of RSV. No additive effects between RSV and energy restriction were observed. © 2017 BioFactors, 43(3):371-378, 2017.

Limited beneficial effects of piceatannol supplementation on obesity complications in the obese Zucker rat: gut microbiota, metabolic, endocrine, and cardiac aspects.

Resveratrol is beneficial in obese and diabetic rodents. However, its low bioavailability raises questions about its therapeutic relevance for treating or preventing obesity complications. In this context, many related natural polyphenols are being tested for their putative antidiabetic and anti-obesity effects. This prompted us to study the influence of piceatannol, a polyhydroxylated stilbene, on the prevention of obesity complications in Zucker obese rats. A 6-week supplementation was followed by the determination of various markers in plasma, liver, adipose tissue and heart, together with a large-scale analysis of gut microbiota composition. When given in doses of 15 or 45 mg/kg body weight/day, piceatannol did not reduce either hyperphagia or fat accumulation. It did not modify the profusion of the most abundant phyla in gut, though slight changes were observed in the abundance of several Lactobacillus, Clostridium, and Bacteroides species belonging to Firmicutes and Bacteroidetes. This was accompanied by a tendency to reduce plasma lipopolysaccharides by 30 %, and by a decrease of circulating non-esterified fatty acids, LDL-cholesterol, and lactate. While piceatannol tended to improve lipid handling, it did not mitigate hyperinsulinemia and cardiac hypertrophy. However, it increased cardiac expression of ephrin-B1, a membrane protein that contributes to maintaining cardiomyocyte architecture. Lastly, ascorbyl radical plasma levels and hydrogen peroxide release by adipose tissue were similar in control and treated groups. Thus, piceatannol did not exhibit strong slimming capacities but did limit several obesity complications.

MicroRNAs involved in the browning process of adipocytes.

The present review focuses on the role of miRNAs in the control of white adipose tissue browning, a process which describes the recruitment of adipocytes showing features of brown adipocytes in white adipose tissue. MicroRNAs (miRNAs) are a class of short non-coding RNAs (19-22 nucleotides) involved in gene regulation. Although the main effect of miRNAs is the inhibition of the translational machinery, thereby preventing the production of the protein product, the activation of protein translation has also been described in the literature. In addition to modifying translation, miRNAs binding to its target mRNAs also trigger the recruitment and association of mRNA decay factors, leading to mRNA destabilization, degradation, and thus to the decrease in expression levels. Although a great number of miRNAs have been reported to potentially regulate genes that play important roles in the browning process, only a reduced number of studies have demonstrated experimentally an effect on this process associated to changes in miRNA expressions, so far. These studies have shown, by using either primary adipocyte cultures or experimental models of mice (KO mice, mice overexpressing a specific miRNA), that miR-196a, miR-26, and miR-30 are needed for browning process development. By contrast, miR-155, miR-133, miR-27b, and miR-34 act as negative regulators of this process [corrected]. Further studies are needed to fully describe the miRNA network-involved white adipose tissue browning regulation.

Pterostilbene improves glycaemic control in rats fed an obesogenic diet: involvement of skeletal muscle and liver.

This study aims to determine whether pterostilbene improves glycaemic control in rats showing insulin resistance induced by an obesogenic diet. Rats were divided into 3 groups: the control group and two groups treated with either 15 mg kg(-1) d(-1) (PT15) or 30 mg kg(-1) d(-1) of pterostilbene (PT30). HOMA-IR was decreased in both pterostilbene-treated groups, but this reduction was greater in the PT15 group (-45% and -22% respectively vs. the control group). The improvement of glycaemic control was not due to a delipidating effect of pterostilbene on skeletal muscle. In contrast, GLUT4 protein expression was increased (+58% and +52% vs. the control group), suggesting an improved glucose uptake. The phosphorylated-Akt/total Akt ratio was significantly enhanced in the PT30 group (+25%), and therefore a more efficient translocation of GLUT4 is likely. Additionally, in this group the amount of cardiotrophin-1 was significantly increased (+65%). These data suggest that the effect of pterostilbene on Akt is mediated by this cytokine. In the liver, glucokinase activity was significantly increased only in the PT15 group (+34%), and no changes were observed in glucose-6-phosphatase activity. The beneficial effect of pterostilbene on glycaemic control was more evident with the lower dose, probably because in the PT15 group both the muscle and the liver were contributing to this effect, but in the PT30 group only the skeletal muscle was responsible. In conclusion, pterostilbene improves glycaemic control in rats showing insulin resistance induced by an obesogenic diet. An increase in hepatic glucokinase activity, as well as in skeletal muscle glucose uptake, seems to be involved in the anti-diabetic effect of this phenolic compound.

Impact of intermittent hypoxia and exercise on blood pressure and metabolic features from obese subjects suffering sleep apnea-hypopnea syndrome.

Strategies designed to reduce adiposity and cardiovascular-accompanying manifestations have been based on nutritional interventions conjointly with physical activity programs. The aim of this 13-week study was to investigate the putative benefits associated to hypoxia plus exercise on weight loss and relevant metabolic and cardiorespiratory variables, when prescribed to obese subjects with sleep apnea syndrome following dietary advice. The participants were randomly distributed in the following three groups: control, normoxia, and hypoxia. All the subjects received dietary advice while, additionally, normoxia group was trained under normal oxygen concentration and Hypoxia group under hypoxic conditions. There was a statistically significant decrease in fat-free mass (Kg) and water (%) on the control compared to normoxia group (p < 0.05 and p < 0.01, respectively). Body weight, body mass index, and waist circumference decreased in all the groups after the study. Moreover, leukocyte count was increased after the intervention in hypoxia compared to control group (p < 0.05). There were no statistically significant variations within groups in other variables, although changes in appetite were found after the 13-week period. In addition, associations between the variations in the leukocyte count and fat mass have been found. The hypoxia group showed some specific benefits concerning appetite and cardiometabolic-related measurements as exertion time and diastolic blood pressure, with a therapeutical potential.

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 they 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 randomised into four groups fed an HFS diet supplemented or not with trans-resveratrol [15 mg/kg body weight (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 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 the intestinal level, altering the mRNA expression of tight-junction proteins and inflammation-associated genes.

Potential application of non-flavonoid phenolics in diabetes: antiinflammatory effects.

Polyphenols are members of a very large family of plant-derived compounds that may have beneficial effects on human health, and thus their study has become an increasingly important area of human nutrition research. Considering that it is increasingly accepted that chronic sub-acute inflammation plays an important role in the development of insulin resistance and of diabetes in animals and in humans, the aim of the present review is to compile information concerning the anti-inflammatory effects of non-flavonoid polyphenols on diabetes prevention and/or treatment. Most of these studies have been carried out with different cultured cells and using animal models displaying different types of diabetes, such as diabetes induced by streptozotocin or streptozotocin-nicotinamide, genetic diabetes or diabetes induced by high-fat feeding. In general terms, non-flavonoid polyphenols reduce the production of inflammatory mediators, such as IL-1ß, IL-8, MCP-1, COX-2 or iNOS in these animal models of diabetes. This effect is accompanied in the vast majority of these studies by improved insulin action. In addition, some of the non-flavonoid polyphenols are also able to ameliorate or prevent several pathological alterations associated with the development of diabetes, such as nephropathy, cardiopathy or retinopathy. Very little information has been reported with regard to human studies to date. Thus, new studies are needed to confirm if the beneficial effects observed in preclinical studies can apply to human beings.

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, can be manipulated by diet and dietary components. Feeding animals with high-fat sucrose (HFS) 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 male Wistar rats fed a HFS diet for 6 weeks and compare it with the basal microbial composition. For this purpose, DNA extracted from faeces at baseline and after treatment was analysed by amplification of the V4-V6 region of the 16S ribosomal DNA (rDNA) gene using 454 pyrosequencing. Short-chain fatty acids, i.e. acetate, propionate and butyrate, were also evaluated by gas chromatography-mass spectrometry. 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, the class Clostridia showed a significant decrease after 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 characterising gut microbial population differences at species level and contribute to understand the plausible link between diet and specific gut bacterial species that are able to influence the inflammatory status, intestinal barrier function and obesity development.

Comparative effect of two Mediterranean diets versus a low-fat diet on glycaemic control in individuals with type 2 diabetes.

BACKGROUND/OBJECTIVES: Although benefits have been attributed to the Mediterranean diet, its effect on glycaemic control has not been totally elucidated. The aim of this work was to compare the effect of two Mediterranean diets versus a low-fat diet on several parameters and indices related to glycaemic control in type 2 diabetic subjects. SUBJECTS/METHODS: A multicentric parallel trial was conducted on 191 participants (77 men and 114 women) of the PREDIMED study in order to compare three dietary interventions: two Mediterranean diets supplemented with virgin olive oil (n=67; body mass index (BMI)=29.4±2.9) or mixed nuts (n=74; BMI=30.1±3.1) and a low-fat diet (n=50; BMI=29.8±2.8). There were no drop-outs. Changes in body weight and waist circumference were determined. Insulin resistance was measured by HOMA-IR index, adiponectin/leptin and adiponectin/HOMA-R ratios after 1 year of follow-up. RESULTS: Increased values of adiponectin/leptin ratio (P=0.043, P=0.001 and P<0.001 for low-fat, olive oil and nut diets, respectively) and adiponectin/HOMA-IR ratio (P=0.061, P=0.027 and P=0.069 for low-fat, olive oil and nut diets, respectively) and decreased values of waist circumference (P=0.003, P=0.001 and P=0.001 for low-fat, olive oil and nut diets, respectively) were observed in the three groups. In both Mediterranean diet groups, but not in the low-fat diet group, this was associated with a significant reduction in body weight (P=0.347, P=0.003 and P=0.021 for low-fat, olive oil and nut diets, respectively). CONCLUSIONS: Mediterranean diets supplemented with virgin olive oil or nuts reduced total body weight and improved glucose metabolism to the same extent as the usually recommended low-fat diet.

Quercetin can reduce insulin resistance without decreasing adipose tissue and skeletal muscle fat accumulation.

Quercetin exhibits a wide range of biological functions. The first aim of the present work was to analyze the effects of quercetin on fat accumulation in adipose tissue and glycemic control in rats. Any potential involvement of muscle fatty acid oxidation in its effect on glycemic control was also assessed. Animals were fed a high-fat high-sucrose diet either supplemented with quercetin (30 mg/kg body weight/day), or not supplemented, for 6 weeks. One week before killing, a glucose tolerance test was carried out. Muscle triacylglycerol content, serum glucose, insulin, fructosamine and free fatty acids were measured, and homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. The activities of lipogenic enzymes and lipoprotein lipase in adipose tissue, carnitine palmitoyl transferase-1b (CPT-1b) and citrate synthase in skeletal muscle, and the expression of several genes, ACO, CD36, CPT-1b, PPAR-α, PGC-1α, UCP3, TFAM and COX-2 in skeletal muscle were analyzed. Quercetin caused no significant reduction in body weight or adipose tissue sizes. However, fructosamine, basal glucose and insulin, and consequently HOMA-IR, were significantly reduced by quercetin. No changes were observed in the activity of lipogenic enzymes and lipoprotein lipase. Muscle triacylglycerol content was similar in both experimental groups. The expression of ACO, CD36, CPT-1b, PPAR-α, PGC-1α, UCP3, TFAM and COX-2 remained unchanged. It can be concluded that quercetin is more effective as an anti-diabetic than as an anti-obesity biomolecule. The improvement in insulin resistance induced by this flavonoid is not mediated by a delipidating effect in skeletal muscle.