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Genetic Depletion of Adipocyte Creatine Metabolism Inhibits Diet-Induced Thermogenesis and Drives Obesity.

Authors: Kazak, Lawrence  Chouchani, Edward T  Lu, Gina Z  Jedrychowski, Mark P  Bare, Curtis J  Mina, Amir I  Kumari, Manju  Zhang, Song  Vuckovic, Ivan  Laznik-Bogoslavski, Dina  Dzeja, Petras  Banks, Alexander S  Rosen, Evan D  Spiegelman, Bruce M 
Citation: Kazak L, etal., Cell Metab. 2017 Oct 3;26(4):660-671.e3. doi: 10.1016/j.cmet.2017.08.009. Epub 2017 Aug 24.
Pubmed: (View Article at PubMed) PMID:28844881
DOI: Full-text: DOI:10.1016/j.cmet.2017.08.009

Diet-induced thermogenesis is an important homeostatic mechanism that limits weight gain in response to caloric excess and contributes to the relative stability of body weight in most individuals. We previously demonstrated that creatine enhances energy expenditure through stimulation of mitochondrial ATP turnover, but the physiological role and importance of creatine energetics in adipose tissue have not been explored. Here, we have inactivated the first and rate-limiting enzyme of creatine biosynthesis, glycine amidinotransferase (GATM), selectively in fat (Adipo-Gatm KO). Adipo-Gatm KO mice are prone to diet-induced obesity due to the suppression of elevated energy expenditure that occurs in response to high-calorie feeding. This is paralleled by a blunted capacity for ß3-adrenergic activation of metabolic rate, which is rescued by dietary creatine supplementation. These results provide strong in vivo genetic support for a role of GATM and creatine metabolism in energy expenditure, diet-induced thermogenesis, and defense against diet-induced obesity.

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RGD Object Information
RGD ID: 13673791
Created: 2018-06-23
Species: All species
Last Modified: 2018-06-23
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.