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 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.

中文翻译：

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脂肪细胞肌酸代谢的遗传耗竭抑制饮食诱导的产热并导致肥胖。

饮食诱导的产热是一种重要的体内平衡机制，它限制了因热量过剩而导致的体重增加，并有助于大多数人的体重相对稳定。我们之前已经证明肌酸通过刺激线粒体 ATP 转换来增强能量消耗，但尚未探索肌酸能量在脂肪组织中的生理作用和重要性。在这里，我们选择性地在脂肪中灭活了肌酸生物合成的第一个限速酶甘氨酸脒基转移酶 (GATM) (Adipo-Gatm KO)。Adipo-Gatm KO 小鼠容易发生饮食诱导的肥胖，因为高热量喂养引起的能量消耗升高受到抑制。这与 β3-肾上腺素能激活代谢率的能力减弱相平行，这是通过膳食肌酸补充剂挽救的。这些结果为 GATM 和肌酸代谢在能量消耗、饮食诱导的产热和饮食诱导的肥胖防御中的作用提供了强有力的体内遗传支持。