Intestinal microbiota changes are associated with the development of obesity. However, studies in humans have generated conflicting results due to high inter-individual heterogeneity in terms of diet, age, and hormonal factors, and the largely unexplored influence of gender. In this work, we aimed to identify differential gut microbiota signatures associated with obesity, as a function of gender and changes in body mass index (BMI). Differences in the bacterial community structure were analyzed by 16S sequencing in 39 men and 36 post-menopausal women, who had similar dietary background, matched by age and stratified according to the BMI. We observed that the abundance of the Bacteroides genus was lower in men than in women (P<0.001, Q = 0.002) when BMI was > 33. In fact, the abundance of this genus decreased in men with an increase in BMI (P<0.001, Q<0.001). However, in women, it remained unchanged within the different ranges of BMI. We observed a higher presence of Veillonella (84.6% vs. 47.2%; X2 test P = 0.001, Q = 0.019) and Methanobrevibacter genera (84.6% vs. 47.2%; X2 test P = 0.002, Q = 0.026) in fecal samples in men compared to women. We also observed that the abundance of Bilophila was lower in men compared to women regardless of BMI (P = 0.002, Q = 0.041). Additionally, after correcting for age and sex, 66 bacterial taxa at the genus level were found to be associated with BMI and plasma lipids. Microbiota explained at P = 0.001, 31.17% variation in BMI, 29.04% in triglycerides, 33.70% in high-density lipoproteins, 46.86% in low-density lipoproteins, and 28.55% in total cholesterol. Our results suggest that gut microbiota may differ between men and women, and that these differences may be influenced by the grade of obesity. The divergence in gut microbiota observed between men and women might have a dominant role in the definition of gender differences in the prevalence of metabolic and intestinal inflammatory diseases.

OBJECTIVE-Using the genome-wide association approach, we recently identified the glucokinase regulatory protein gene (GCKR, rs780094) region as a novel quantitative trait locus for plasma triglyceride concentration in Europeans. Here, we sought to study the association of GCKR variants with metabolic phenotypes, including measures of glucose homeostasis, to evaluate the GCKR locus in samples of non-European ancestry and to finemap across the associated genomic interval.RESEARCH DESIGN AND METHODS-We performed association studies in 12 independent cohorts comprising Ͼ45,000 individuals representing several ancestral groups (whites from Northern and Southern Europe, whites from the U.S., African Americans from the U.S., Hispanics of Caribbean origin, and Chinese, Malays, and Asian Indians from Singapore). We conducted genetic fine-mapping across the ϳ417-kb region of linkage disequilibrium spanning GCKR and 16 other genes on chromosome 2p23 by imputing untyped HapMap single nucleotide polymorphisms (SNPs) and genotyping 104 SNPs across the associated genomic interval.RESULTS-We provide comprehensive evidence that GCKR rs780094 is associated with opposite effects on fasting plasma triglyceride (P meta ϭ 3 ϫ 10 Ϫ56) and glucose (P meta ϭ 1 ϫ 10 Ϫ13 ) concentrations. In addition, we confirmed recent reports that the same SNP is associated with C-reactive protein (CRP) level (P ϭ 5 ϫ 10 Ϫ5). Both fine-mapping approaches revealed a common missense GCKR variant (rs1260326, Pro446Leu, 34% frequency, r 2 ϭ 0.93 with rs780094) as the strongest association signal in the region.CONCLUSIONS-These findings point to a molecular mechanism in humans by which higher triglycerides and CRP can be coupled with lower plasma glucose concentrations and position GCKR in central pathways regulating both hepatic triglyceride and glucose metabolism. Diabetes 57:3112-3121, 2008

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This study evaluated the possible prebiotic effect of a moderate intake of red wine polyphenols on the modulation of the gut microbiota composition and the improvement in the risk factors for the metabolic syndrome in obese patients. Ten metabolic syndrome patients and ten healthy subjects were included in a randomized, crossover, controlled intervention study. After a washout period, the subjects consumed red wine and de-alcoholized red wine over a 30 day period for each. The dominant bacterial composition did not differ significantly between the study groups after the two red wine intake periods. In the metabolic syndrome patients, red wine polyphenols significantly increased the number of fecal bifidobacteria and Lactobacillus (intestinal barrier protectors) and butyrate-producing bacteria (Faecalibacterium prausnitzii and Roseburia) at the expense of less desirable groups of bacteria such as LPS producers (Escherichia coli and Enterobacter cloacae). The changes in gut microbiota in these patients could be responsible for the improvement in the metabolic syndrome markers. Modulation of the gut microbiota by using red wine could be an effective strategy for managing metabolic diseases associated with obesity.

Introduction: Cardiovascular disease remains the commonest health problem in developed countries, and residual risk after implementing all current therapies is still high. The use of marine omega-3 fatty acids (DHA and EPA) has been recommended to reduce cardiovascular risk by multiple mechanisms. Objectives: To update the current evidence on the influence of omega-3 on the rate of cardiovascular events. Review Methods: We used the MEDLINE and EMBASE databases to identify clinical trials and randomized controlled trials of omega-3 fatty acids (with quantified quantities) either in capsules or in dietary intake, compared to placebo or usual diet, equal to or longer than 6 months, and written in English. The primary outcome was a cardiovascular event of any kind and secondary outcomes were all-cause mortality, cardiac death and coronary events. We used RevMan 5·1 (Mantel-Haenszel method). Heterogeneity was assessed by the I 2 and Chi 2 tests.

Our results suggest that long-term consumption of the Med and LFHCC diets exerts a protective effect on the development of type 2 diabetes by different specific changes in the gut microbiota, increasing the abundance of the Roseburia genus and F. prausnitzii, respectively.

OBJECTIVE -Central obesity is associated with insulin resistance through factors that are not fully understood. We studied the effects of three different isocaloric diets on body fat distribution, insulin sensitivity, and peripheral adiponectin gene expression. RESEARCH DESIGN AND METHODS-Eleven volunteers, offspring of obese type 2 diabetic patients with abdominal fat deposition, were studied. These subjects were considered insulin resistant as indicated by Matsuda index values Ͻ4 after an oral glucose tolerance test, and they maintained A1C Ͻ6.5% without therapeutic intervention. All subjects underwent three dietary periods of 28 days each in a crossover design: 1) diet enriched in saturated fat (SAT), 2) diet rich in monounsaturated fat (MUFA) (Mediterranean diet), and 3) diet rich in carbohydrates (CHOs).RESULTS -Weight, body composition, and resting energy expenditure remained unchanged during the three sequential dietary periods. Using dual-energy X-ray absorptiometry we observed that when patients were fed a CHO-enriched diet, their fat mass was redistributed toward the abdominal depot, whereas periphery fat accumulation decreased compared with isocaloric MUFA-rich and high-SAT diets (ANOVA P Ͻ 0.05). Changes in fat deposition were associated with decreased postprandial mRNA adiponectin levels in peripheral adipose tissue and lower insulin sensitivity index values from a frequently sampled insulin-assisted intravenous glucose tolerance test in patients fed a CHO-rich diet compared with a MUFA-rich diet (ANOVA P Ͻ 0.05).CONCLUSIONS -An isocaloric MUFA-rich diet prevents central fat redistribution and the postprandial decrease in peripheral adiponectin gene expression and insulin resistance induced by a CHO-rich diet in insulin-resistant subjects. Diabetes Care 30:1717-1723, 2007A positive energy balance, which leads to obesity, is associated with insulin resistance and an increased risk of type 2 diabetes. According to our studies in rodents, adipose tissue expandability seems to be a key determinant linking obesity and its associated complications (1,2). Expansion of the intra-abdominal depot has been associated with increased insulin resistance, as well as with an increased incidence of fatty liver and ␤-cell failure (3,4).The factors that regulate body fat distribution are not well understood. We hypothesize that the specific macronutrient composition of the diet may be an important environmental factor that controls nutrient partitioning to specific adipose tissue depots (5). It is now well established that adipose tissue is not simply an energy storage organ but is, in fact, the "largest" endocrine gland controlling energy homeostasis (6). It is conceivable that specific diet composition may directly influence the molecular events that govern gene expression in adipocytes (7), adipokine production, and adipocyte lipid and glucose metabolism (8).Adiponectin adipocyte-secreted adipokine plays an important role in modulating insulin sensitivity and concentrations of circulating plasma glucose and noneste...

Olive oil is the most representative food in the traditional Mediterranean diet and its most important source of MUFA. The healthy benefits of MUFA-rich diets on plasma cholesterol levels, were the first to generate interest in this dietary model. In addition to the benefits conferred by its lipids, olive oil has other biological effects, some of them also related to MUFA. However, most recent studies have shown that there are a number of properties that depend on, or are potentiated by, the consumption of olive oil, such as virgin olive oil, that is rich in microcomponents. This foodstuff, thanks to its double set of benefits, thus tends to produce a better lipid profile and a less prothrombotic environment, promoting antioxidant and anti-inflammatory effects, with a greater endothelial protective capacity. In view of these effects, it would appear that when olive oil is the basic source of dietary alimentary fat it has a major antiatherogenic capacity, which is not shared to the same extent by other oils that are rich in oleic acid but lack its characteristic micronutrients.