Mechanisms of Obesity and Its Metabolic Complications in Youth.

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Childhood obesity has become a worldwide phenomenon occurring in about 43 million children and adolescents. Recent studies suggest that gut microbiota contribute to the obese phenotype probably by modulating energy intake through the formation of short chain fatty acids (SCFA) (acetate, propionate, and butyrate). Given the paucity of human data, we have recently started investigating this topic. Our preliminary data generated studying a group of lean and obese children and adolescents demonstrate that: 1) there is a strong association between plasma SCFA and the degree of obesity; 2) the circulating levels of SCFA are related to the synthetic rates of hepatic de novo lipogenesis; and 3) the gut microbiota of obese subjects have a greater ability to ferment carbohydrates than the gut microbiota of lean subjects. Based on these data we hypothesize that obese children and adolescents experience a higher amount of energy harvest for an equal amount of dietary calories than lean, as result of the higher ability of their gut microbiota to synthetize SCFA, which in turn provides an extra source of energy by serving as substrates for hepatic lipogenesis. In order to demonstrate this hypothesis and fill the knowledge void concerning the role of SCFA in the pathophysiology of childhood obesity, we will test the differences in the synthetic rates of SCFA between obese and lean adolescents, and determine how the synthetic rates of SCFA might affect hepatic lipogenesis.