a mouse model for the metabolic effects of the human fat mass and obesity associated fto gene小鼠模型的代谢影响人类脂肪量和肥胖相关的fto基因.pdfVIP

A Mouse Model for the Metabolic Effects of the Human Fat Mass and Obesity Associated FTO Gene 1 2. 3. 2. 4 Chris Church , Sheena Lee , Eleanor A. L. Bagg , James S. McTaggart , Robert Deacon , Thomas 3 1 1 ´3 1 3 Gerken , Angela Lee , Lee Moir , Jasmin Mecinovic , Mohamed M. Quwailid , Christopher J. Schofield , 2 1 Frances M. Ashcroft , Roger D. Cox * 1 MRC Harwell, Metabolism and Inflammation, Harwell Science and Innovation Campus, Harwell, United Kingdom, 2 Henry Wellcome Centre for Gene Function, Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, United Kingdom, 3 Chemistry Research Laboratory and Oxford Centre for Integrative Systems Biology, University of Oxford, Oxford, United Kingdom, 4 Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom Abstract Human FTO gene variants are associated with body mass index and type 2 diabetes. Because the obesity-associated SNPs are intronic, it is unclear whether changes in FTO expression or splicing are the cause of obesity or if regulatory elements within intron 1 influence upstream or downstream genes. We tested the idea that FTO itself is involved in obesity. We show that a dominant point mutation in the mouse Fto gene results in reduced fat mass, increased energy expenditure, and unchanged physical activity. Exposure to a high-fat diet enhances lean mass and lowers fat mass relative to control mice. Biochemical studies