Wanders Desiree, Forney Laura A, Stone Kirsten P, Burk David H, Pierse Alicia, Gettys Thomas W
Department of Nutrition, Georgia State University, Atlanta, GA.
Laboratory of Nutrient Sensing and Adipocyte Signaling, Pennington Biomedical Research Center, Baton Rouge, LA.
Diabetes. 2017 Apr;66(4):858-867. doi: 10.2337/db16-1212. Epub 2017 Jan 17.
Dietary methionine restriction (MR) produces a rapid and persistent remodeling of white adipose tissue (WAT), an increase in energy expenditure (EE), and enhancement of insulin sensitivity. Recent work established that hepatic expression of FGF21 is robustly increased by MR. mice were used to test whether FGF21 is an essential mediator of the physiological effects of dietary MR. The MR-induced increase in energy intake and EE and activation of thermogenesis in WAT and brown adipose tissue were lost in mice. However, dietary MR produced a comparable reduction in body weight and adiposity in both genotypes because of a negative effect of MR on energy intake in mice. Despite the similar loss in weight, dietary MR produced a more significant increase in in vivo insulin sensitivity in wild-type than in mice, particularly in heart and inguinal WAT. In contrast, the ability of MR to regulate lipogenic and integrated stress response genes in liver was not compromised in mice. Collectively, these findings illustrate that FGF21 is a critical mediator of the effects of dietary MR on EE, remodeling of WAT, and increased insulin sensitivity but not of its effects on hepatic gene expression.
饮食蛋氨酸限制（MR）可使白色脂肪组织（WAT）迅速且持续重塑，增加能量消耗（EE），并增强胰岛素敏感性。最近的研究表明，MR可使肝脏中FGF21的表达显著增加。使用小鼠来测试FGF21是否是饮食MR生理效应的关键介质。在小鼠中，MR诱导的能量摄入增加、EE增加以及WAT和棕色脂肪组织中产热的激活均消失。然而，由于MR对小鼠能量摄入的负面影响，饮食MR在两种基因型小鼠中均使体重和肥胖程度出现了类似程度的降低。尽管体重下降程度相似，但饮食MR在野生型小鼠中比在小鼠中使体内胰岛素敏感性有更显著的增加，尤其是在心脏和腹股沟WAT中。相比之下，MR调节肝脏中脂肪生成和整合应激反应基因的能力在小鼠中并未受损。总体而言，这些发现表明，FGF21是饮食MR对EE、WAT重塑和胰岛素敏感性增加影响的关键介质，但不是其对肝脏基因表达影响的关键介质。
