Molecular phenomics of a high-calorie diet-induced porcine model of prepubertal obesity.

As obesity incidence is alarmingly rising among young individuals, we aimed to characterize an experimental model of this situation, considering the similarity between human and porcine physiology. For this reason, we fed prepubertal (63 days old) Duroc breed females (n=21) either with a standard growth diet (3800 kcal/day) or one with a high-calorie content (5200 kcal/day) during 70 days. Computerized tomography, mass-spectrometry-based metabolomics and lipidomics, as well as peripheral blood mononuclear cell transcriptomics, were applied to define traits linked to high-calorie intake. Samples from a human cohort confirmed potential lipidomic markers. Compared to those fed a standard growth diet, pigs fed a high-calorie diet showed an increased weight gain (13%), much higher adiposity (53%), hypertriacylglyceridemia and hypercholesterolemia in parallel to insulin resistance. This diet induced marked changes in the circulating lipidome, particularly in phosphatidylethanolamine-type molecules. Also, circulating specific diacylglycerol and monoacylglycerol contents correlated with visceral fat and intrahepatic triacylglycerol concentrations. Specific lipids associated with obesity in swine (mainly belonging to glycerophospholipid, triacylglyceride and sterol classes) were also linked with obesity traits in the human cohort, reinforcing the usefulness of the chosen approach. Interestingly, no overt inflammation in plasma or adipose tissue was evident in this model. The presented model is useful as a preclinical surrogate of prepubertal obesity in order to ascertain the pathophysiology interactions between energy intake and obesity development.

Bioactivity of Flavonoids on Insulin-Secreting Cells.

Flavonoids are usually found in fruits and other plant organs and therefore widely consumed. They are antioxidants, anti-inflammatory, anticarcinogenic, and protective against coronary disease and metabolic disorders. These beneficial effects make them good candidates for the development of new functional foods with potential protective/preventive properties against several diseases. We must consider that this fact could lead to a higher intake of some of these flavonoids. Most of the studies concerning their beneficial effects showed peripheral activity of these molecules, but there is no clear information about their central effects on a key organ on metabolic control: the endocrine pancreas. The pancreas has an endocrine function of major importance to regulate nutrient metabolism, such as control of glucose homeostasis via insulin and glucagon secretion. Its importance in whole body nutrient equilibrium is highlighted by the fact that several pathologies, such as type 1 and/or 2 diabetes, are related at some point to a pancreatic cell deregulation. In this review, we compile the most relevant results concerning the effects of flavonoids on several aspects of pancreatic functionality. Studies using animals with drug-induced diabetes support the hypothesis that flavonoids can ameliorate this pathogenesis. The great diversity of flavonoid structures makes it difficult to establish common effects in the pancreas. Published data suggest that there might be direct effects of flavonoids on insulin secretion, as well as on prevention of beta-cell apoptosis, and they could even act via modulation of proliferation. The mechanisms of action involve mainly their antioxidant properties, but other pathways might also take place.