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BackgroundThe expression of some genes controlling energy homeostasis could be regulated by epigenetic mechanisms that may play a role in body weight regulation. Thus, it is known that various nutritional factors affect DNA methylation. In order to assess whether the macronutrient composition of the diet could be related to the epigenetic regulation of gene expression and with obesity development, we investigated the effects on methylation and expression patterns of two pair-fed isocaloric diets in rats: control (rich in starch) and HFS (rich in fat and sucrose).ResultsThe pair-fed HFS diet induced higher weight gain and adiposity as compared to the controls as well as liver triglyceride accumulation and oxidative stress. Feeding the HFS diet impaired glucose tolerance and serum triglycerides and cholesterol. Liver glucokinase expression, a key glycolytic gene, remained unaltered, as well as the mRNA values of fatty acid synthase and NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 6 (NDUFB6) in liver and visceral adipocytes, which regulate lipogenesis and mitochondrial oxidative metabolism, respectively. Liver expression of hydroxyacyl-coenzyme A dehydrogenase (HADHB), a key gene of β-oxidation pathway, was higher in the HFS-fed animals. However, the methylation status of CpG islands in HADHB and glucokinase genes remained unchanged after feeding the HFS diet.ConclusionsThese results confirm that the distribution and type of macronutrients (starch vs. sucrose, and percent of fat) influence obesity onset and the associated metabolic complications. HFS diets produce obesity independently of total energy intake, although apparently no epigenetic (DNA methylation) changes accompanied the modifications observed in gene expression.

Chronic mild stress (CMS) has been often associated to the pathogenesis of many diseases including obesity. Indeed, visceral obesity has been linked to the development of metabolic syndrome features and constitutes a serious risk factor for cardiovascular diseases and diabetes. In order to study possible mechanistic relationships between stress and the onset of obesity, we developed during 11 weeks a model of high-fat dietary intake (cafeteria diet) together with a CMS regimen in male Wistar rats. During the experimental period, basal metabolism by indirect calorimetry, rectal temperature, food intake, and locomotive markers were specifically analyzed. After 77 days, animals were sacrificed and body, adiposity and plasma biochemical profiles were also examined. As expected, cafeteria diet in unstressed animals induced a significative increase in body weight, adiposity, and insulin resistance markers. Locomotive variables, specifically distance, rearing and meander, were significantly increased by CMS on the first weeks of stress. Moreover, this model of CMS in Wistar rats increased significantly energy expenditure, and apparently interplayed with the dietary treatment on the muscle weight/fat weight ratio. In summary, this chronic stress model did not affected weight gain in control and high fat fed animals, but induced an interaction concerning the metabolic muscle/fat repartitioning.

Background/Aim: Changes in dietary macronutrient content are involved in altered energy metabolism and obesity development. However, there are controversial views about the obesogenic effects of high-sucrose (HS) diets, which usually lead to obesity and insulin resistance but are sometimes associated with reduced weight gain. The aim of this study was to investigate the effect of consumption of a pair-fed HS diet on weight gain and energy homeostasis in rats, as well as to assess the effects on expression of the NADH dehydrogenase (ubiquinone) 1β subcomplex 6 (NDUFB6) gene in adipose tissue. Methods/Results: Although both dietary groups, i.e. HS and control, were pair-fed (isoenergetic feeding), the HS diet increased adiposity and decreased plasma total and high-density lipoprotein cholesterol levels. While no significant differences were found with regard to serum glucose, insulin, adiponectin, free fatty acids and liver malondialdehyde, a slight increase in serum and liver triglycerides was observed. Interestingly, the gene expression of NDUFB6, an inner mitochondrial membrane protein involved in mitochondrial electron transport, was reduced in epididymal adipose tissue when compared to the control-fed group. Conclusion: These results suggest, apparently for the first time, that high-sugar diets appear to induce mitochondrial dysfunction in adipose tissue, which may be related to greater weight gain and metabolic impairment.

The combination of vanadate plus benzylamine has been reported to stimulate glucose transport in rodent adipocytes and to mimic other insulin actions in diverse studies. However, benzylamine alone activates glucose uptake in human fat cells and increases glucose tolerance in rabbits. The aim of this work was to unravel the benzylamine antihyperglycemic action and to test whether its chronic oral administration could restore the defective glucose handling of mice rendered slightly obese and diabetic by very high-fat diet (VHFD). When VHFD mice were i.p. injected with benzylamine at 0.7 to 700 micromol/kg before glucose tolerance test, they exhibited reduced hyperglycemic response without alteration of insulin secretion. Whole body glucose turnover, as assessed by the glucose isotopic dilution technique, was unchanged in mice perfused with benzylamine (total dose of 75 micromol/kg). However, their in vivo glycogen synthesis rate was increased. Benzylamine appeared therefore to directly facilitate glucose utilisation in peripheral tissues. When given chronically at 2000 or 4000 micromol/kg/d in drinking water, benzylamine elicited a slight reduction of water consumption but did not change body weight or adiposity and did not modify oxidative stress markers. Benzylamine treatment improved glucose tolerance but failed to normalize the elevated glucose fasting plasma levels of VHFD mice. There was no influence of benzylamine ingestion on lipolytic activity, basal and insulin-stimulated glucose uptake, and on inflammatory adipokine expression in adipocytes. The improvement of glucose tolerance and the lack of adverse effects on adipocyte metabolism, reported here in VHFD mice allow to consider orally given benzylamine as a potential antidiabetic strategy which deserves to be further studied in other diabetic models.