Genetic Depletion of Adipocyte Creatine Metabolism Inhibits Diet-Induced Thermogenesis and Drives Obesity.
Genetic Depletion of Adipocyte Creatine Metabolism Inhibits Diet-Induced Thermogenesis and Drives Obesity.
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DOI：
10.1016/j.cmet.2017.08.009
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发表时间：
2017-10-03
期刊：
影响因子：
29
通讯作者：
Spiegelman BM
中科院分区：
文献类型：
--
作者：
Kazak L;Chouchani ET;Lu GZ;Jedrychowski MP;Bare CJ;Mina AI;Kumari M;Zhang S;Vuckovic I;Laznik-Bogoslavski D;Dzeja P;Banks AS;Rosen ED;Spiegelman BM
饮食诱导的产热是一种重要的体内平衡机制，它限制了热量过剩时体重的增加，并有助于大多数个体体重的相对稳定。我们之前证明了肌酸通过刺激线粒体ATP的转换来增加能量消耗，但是肌酸在脂肪组织中的生理作用和重要性还没有被探索。在这里，我们选择性地灭活了脂肪中肌酸生物合成的第一酶和限速酶甘氨酸氨基转移酶（GATM） （Adipo-Gatm KO）。Adipo-Gatm KO小鼠容易发生饮食引起的肥胖，因为高热量喂养会抑制能量消耗的增加。这与代谢率β3-肾上腺素能激活的钝化能力是平行的，这是通过膳食补充肌酸来拯救的。这些结果为GATM和肌酸代谢在能量消耗、饮食诱导产热和饮食诱导肥胖防御中的作用提供了强有力的体内遗传支持。XXX等人研究了脂肪组织中限速酶甘氨酸氨基转移酶（GATM）功能丧失对肌酸能量学的生理影响。Adipo-Gatm KO小鼠不能通过能量消耗抵消增加的卡路里而增加体重。它们较低的代谢率可以通过膳食补充肌酸来挽救。
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 has 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 β3-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. XXX et al investigate the physiological effects of creatine energetics through loss of function of the rate-limiting enzyme, glycine amidinotransferase (GATM), in adipose tissue. Adipo-Gatm KO mice cannot counteract increased calories with energy expenditure and gain weight. Their lower metabolic rate can be rescued by dietary creatine supplementation.
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影响因子：
3.5
作者：
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通讯作者：
Isbrandt, Dirk
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作者：
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通讯作者：
Kozak, LP