Mechanisms of Obesity and Its Metabolic Complications in Youth

青少年肥胖及其代谢并发症的机制

• 批准号: 10655170
• 负责人: Nicola Santoro
• 金额: $ 17.92万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-25 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10655170
• 关键词: Acetates; Address; Adolescent; Adolescent obesity; Affect; Automobile Driving; Bacterial Genes; Body fat; Butyrates; Calories; Carbohydrates; Carbon; Child; Chronic Disease; Consumption; Cross-Over Studies; Data; Development; Diet; Dietary Intervention; Energy Intake; Energy-Generating Resources; Exhibits; Fatty Acids; Feces; Fermentation; Functional disorder; Harvest; Hepatic; High Prevalence; Human; In Vitro; Inulin; Knowledge; Liver; Macronutrients Nutrition; Measures; Mediating; Metabolic; Metabolism; Metagenomics; Nutrient; Obesity; Palmitates; Pathogenesis; Pathway interactions; Pediatrics; Peripheral; Phenotype; Plasma; Predisposition; Process; Production; Propionates; Role; Source; Testing; Thinness; Time; Volatile Fatty Acids; Work; Youth; base; dietary; dietary control; energy balance; experience; feeding; gut microbiota; human data; improved; lipid biosynthesis; microbiota; obese person; obesity development; obesity in children

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.

儿童肥胖症已成为一种世界性现象，约有4300万儿童和青少年发生。最近的研究表明，肠道微生物群可能通过形成短链脂肪酸（SCFA）（乙酸盐、丙酸盐和丁酸盐）来调节能量摄入，从而导致肥胖表型。由于缺乏人类数据，我们最近开始研究这个话题。研究一组瘦和肥胖儿童和青少年产生的初步数据表明：1）血浆SCFA与肥胖程度之间存在强相关性; 2）SCFA的循环水平与肝脏从头脂肪生成的合成速率相关; 3）肥胖受试者的肠道微生物群比瘦受试者的肠道微生物群具有更大的发酵碳水化合物的能力。基于这些数据，我们假设肥胖儿童和青少年在等量的饮食卡路里下比瘦的经历更高的能量收获，这是由于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。为了证明这一假设，并填补知识空白的作用，SCFA在儿童肥胖的病理生理学，我们将测试的差异，在合成率的SCFA之间的肥胖和瘦的青少年，并确定如何SCFA的合成率可能会影响肝脏脂肪生成。