Weight Loss and Concomitant Adipose Autophagy in Methionine-Restricted Obese Mice is Not Dependent on Adiponectin or FGF21
Weight Loss and Concomitant Adipose Autophagy in Methionine-Restricted Obese Mice is Not Dependent on Adiponectin or FGF21
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DOI：
10.1002/oby.22763
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发表时间：
2020-04-29
期刊：
影响因子：
6.9
通讯作者：
Ables, Gene P.
中科院分区：
文献类型：
--
作者：
Cooke, Diana;Mattocks, Dwight;Ables, Gene P.
目的寻找抗击肥胖的新方法对提高健康寿命具有重要意义。据推测，蛋氨酸限制(MR)通过减少因能量消耗增加而引起的脂肪组织质量和脂肪组织内稳态的重新编程而导致肥胖小鼠体重减轻。方法采用饮食诱导肥胖(DIO)雄性C57BL/6J(野生型)、ADIPOQ缺陷(ADIPOQ基因敲除[KO])、FGF21-KO和ADIPOQ-FGF21双KO小鼠。在切换到高脂对照(DIO-CF，60%脂肪/0.86%蛋氨酸)或MR(DIO-MR，60%脂肪/0.12%蛋氨酸)饮食后，测量生理参数，并检查腹股沟和肾上腺周围脂肪组织。结果MR组肥胖小鼠体重和脂肪减少，能量消耗增加，糖耐量改善，这与ADIPOQ和FGF21的作用无关。MR可降低循环血脂、血糖、胰岛素、瘦素和胰岛素样生长因子1，增加β-羟丁酸、ADIPOQ和FGF21浓度。在脂肪中，MR上调脂肪甘油三酯脂酶、凋亡诱导因子、溶酶体相关膜蛋白1和2、自噬相关蛋白5、Beclin-1、轻链3B I和II的蛋白水平。结论MR肥胖小鼠脂肪组织质量减少与脂肪分解、细胞凋亡和自噬增加有关，且与ADIPOQ和FGF21的作用无关。
Objective Identifying novel approaches to combat obesity is important to improve health span. It was hypothesized that methionine restriction (MR) will induce weight loss in obese mice by reducing adipose tissue mass caused by increased energy expenditure and reprogramming of adipose tissue homeostasis. The roles of adiponectin (ADIPOQ) and fibroblast growth factor 21 (FGF21) during weight loss in MR mice were also tested.Methods Diet-induced obese (DIO) male C57BL/6J (wild type), Adipoq-deficient (Adipoq knockout [KO]), Fgf21-KO, and Adipoq-Fgf21 double-KO mice were used. Following a switch to high-fat control (DIO-CF, 60% fat/0.86% methionine) or MR (DIO-MR, 60% fat/0.12% methionine) diet, physiological parameters were measured, and inguinal and perigonadal adipose tissues were examined.Results Obese mice subjected to MR showed loss of body weight and adiposity, increased energy expenditure, and improved glucose tolerance that were independent of the actions of ADIPOQ and FGF21. MR induced reduction of circulating lipids, glucose, insulin, leptin, and insulin like growth factor 1 and increased beta-hydroxybutyrate, ADIPOQ, and FGF21 concentrations. In fat, MR upregulated protein levels of adipose triglyceride lipase, apoptosis-inducing factor, lysosomal-associated membrane proteins 1 and 2, autophagy-related protein 5, beclin-1, and light chain 3B I and II.Conclusions MR reduction of adipose tissue mass in obese mice is associated with elevated lipolysis, apoptosis, and autophagy and occurs independently of the actions of ADIPOQ and FGF21.