背景:肌肉生长抑制素(Mstn)在脂肪细胞生长中起重要作用,分化和新陈代谢,导致肥胖的发展。
目的:我们旨在探讨Mstn对2型糖尿病(T2DM)小鼠模型白色脂肪褐变的影响。
方法:十二种野生型(WT),12只杂合(Mstn(+/-))和12只纯合(Mstn(-/-))雄性小鼠随机分为6组:Mstn(+/-),Mstn(-/-),WT+DM,Mstn(+/-)+DM,和Mstn(-/-)+DM。前3组饲喂正常食物,而最后3例喂食高脂饮食并给予链脲佐菌素以产生T2DM。随后,体重,长度,测量白色和棕色脂肪量,之后是李的索引,计算白褐色比率和脂肪指数。采用酶联免疫吸附试验(ELISA)检测血清游离脂肪酸(FFA)水平。苏木精和伊红(H&E)染色用于分析白色和棕色脂肪细胞形态。过氧化物酶体增殖物激活受体γ(PPARγ)的相对表达水平,过氧化物酶体增殖物激活受体-γ辅激活因子-1α(PGC-1α),解偶联蛋白1(UCP1),用蛋白质印迹法测定分化簇137(CD137)蛋白。
结果:Mstn(-/-)组显示出更高水平的PPARγ,与WT和Mstn(+/-)组相比,白色和棕色脂肪中的PGC-1α和CD137蛋白,Mstn(-/-)组UCP1蛋白表达水平高于WT组。PPARγ的表达水平,PGC-1α,WT+DM组的UCP1和CD137蛋白均低于WT组。此外,PPARγ,PGC-1α,与WT+DM和Mstn(+/-)+DM组相比,UCP1和CD137蛋白在Mstn(-/-)+DM组中的表达更高。
结论:Mstn基因抑制拮抗肥胖表型,如2型糖尿病引起的白色脂肪堆积和脂质代谢紊乱,从而促进白色脂肪褐变。
BACKGROUND: Myostatin (Mstn) plays an important role in adipocyte growth, differentiation and metabolism, leading to the development of obesity.
OBJECTIVE: We aimed to explore the effect of Mstn on white fat browning in a mouse model of type 2 diabetes mellitus (T2DM).
METHODS: Twelve wild-type (WT), 12 heterozygous (Mstn(+/-)) and 12 homozygous (Mstn(-/-)) male mice were randomly divided into 6 groups: WT, Mstn(+/-), Mstn(-/-), WT+DM, Mstn(+/-)+DM, and Mstn(-/-)+DM. The first 3 groups were fed normal chow, while the last 3 were fed high-fat diet and administered streptozotocin to generate T2DM. Subsequently, body mass, length, and white and brown fat masses were measured, after which Lee\'s index, white-brown ratio and fat index were calculated. The serum free fatty acid (FFA) levels were detected using enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (H&E) staining was used to analyze white and brown fat cell morphology. The relative expression levels of peroxisome proliferator-activated receptor-gamma (PPARγ), peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), uncoupling protein 1 (UCP1), and cluster of differentiation 137 (CD137) protein were determined with western blotting.
RESULTS: The Mstn(-/-) group displayed higher levels of PPARγ, PGC-1α and CD137 proteins in white and brown fat compared to the WT and Mstn(+/-) groups, while the expression level of UCP1 protein in the Mstn(-/-) group was higher than in the WT group. The expression levels of PPARγ, PGC-1α, UCP1, and CD137 proteins in the WT+DM group were lower than in the WT group. Moreover, PPARγ, PGC-1α, UCP1, and CD137 proteins were more highly expressed in the Mstn(-/-)+DM group compared to the WT+DM and Mstn(+/-)+DM groups.
CONCLUSIONS: The Mstn gene inhibition antagonizes obesity phenotypes, such as white fat accumulation and lipid metabolism derangement caused by T2DM, thus promoting white fat browning.