Mechanisms of Obesity and Its Metabolic Complications in Youth

儿童肥胖已成为一种世界性现象，约有4300万儿童和青少年患有肥胖症。最近的研究表明，肠道微生物区系可能通过形成短链脂肪酸(醋酸、丙酸和丁酸)来调节能量摄入，从而导致肥胖表型。考虑到人类数据的匮乏，我们最近开始研究这个话题。我们对一组瘦身和肥胖的儿童和青少年的初步研究数据表明：1)血浆SCFA与肥胖程度有很强的相关性；2)循环中的SCFA水平与肝脏新生脂肪合成速率有关；3)肥胖者的肠道微生物区系比瘦肉者的肠道微生物区系有更强的碳水化合物发酵能力。基于这些数据，我们假设肥胖的儿童和青少年在等量的饮食卡路里中经历了比瘦肉更高的能量收获，这是因为他们的肠道微生物群合成SCFA的能力更高，这反过来又通过作为肝脏脂肪生成的底物提供了额外的能量来源。为了验证这一假说，填补关于SCFA在儿童肥胖病理生理学中作用的知识空白，我们将测试肥胖和瘦青少年之间SCFA合成速率的差异，并确定SCFA合成速率如何影响肝脏脂肪生成。

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.