Medical Physiology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
J Cell Biochem. 2019 Apr;120(4):5677-5686. doi: 10.1002/jcb.27852. Epub 2018 Oct 15.
A growing interest to understand the signaling pathways mediating obesity-induced muscle atrophy is given. Metformin (Met) was reported to possess positive effects on preventing muscle damage and promoting muscle mass maintenance. The aim of the present study to investigate pathways involved in Met effect on obesity induced muscle atrophy.
Thirty adult male albino rats were assigned into two groups: normal chew diet fed group as control group (C; n = 10) and high-fat-diet (HFD) fed group ( n = 20). After 16 weeks, the HFD-fed animals were subdivided into two groups; HFD group ( n = 10) and HFD fed treated with oral Met (320 mg/day) treatment (Met, n = 10) for 4 weeks. At the end of the experiment; final body weight, visceral fat weight, fasting blood glucose, insulin, lactate, total cholesterol, triglycerides were measured and calculated homeostatic model assessment insulin resistant (HOMA-IR) for all groups. Soleus muscle weight, histopathlogical examination and expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), forkhead box O3 (FoxO3), atrogin-1/MAFbx, and muscle RING finger 1 (MuRF-1) were performed.
HFD-fed animals showed significant increase in final body weight, visceral fat mass, fasting blood glucose, insulin, calculated HOMA-IR, lactate, total cholesterol and triglycerides with significant decrease in soleus muscle weight, PGC-1α and significant increase in FoxO3, atrogin-1/MAFbx, and MuRF-1 expression. Also, there was significant decrease in fiber diameter, myosin heavy chain (MHC) I content while collagen content and myosin heavy chain IIa were increased compared with control group. Met-treated group showed a significant decrease in the measured parameters compared with the HFD group. It also restored the gene expression, morphometric measures and MHC composition toward normal.
The current study is the first to provide evidence that Met could ameliorate muscle atrophy in high-fat diet induced obesity and this effect may be in part due to regulation of PGC-1α-FoxO3 pathway.
人们越来越关注理解介导肥胖引起的肌肉萎缩的信号通路。二甲双胍（Met）已被报道具有预防肌肉损伤和促进肌肉质量维持的积极作用。本研究旨在探讨 Met 对肥胖引起的肌肉萎缩的作用涉及的途径。
将 30 只成年雄性白化大鼠分为两组：正常咀嚼饮食喂养组作为对照组（C；n=10）和高脂肪饮食（HFD）喂养组（n=20）。16 周后，HFD 喂养的动物被分为两组；HFD 组（n=10）和 HFD 喂养的动物接受口服 Met（320mg/天）治疗（Met，n=10）4 周。实验结束时，测量并计算所有组的最终体重、内脏脂肪重量、空腹血糖、胰岛素、乳酸、总胆固醇、甘油三酯，计算稳态模型评估胰岛素抵抗（HOMA-IR）。进行比目鱼肌重量、组织病理学检查以及过氧化物酶体增殖物激活受体-γ共激活因子-1α（PGC-1α）、叉头框 O3（FoxO3）、萎缩基因 1/MAFbx（atrogin-1/MAFbx）和肌肉环指 1（MuRF-1）的表达。
HFD 喂养的动物表现出最终体重、内脏脂肪质量、空腹血糖、胰岛素、计算的 HOMA-IR、乳酸、总胆固醇和甘油三酯的显著增加，而比目鱼肌重量、PGC-1α 和 FoxO3、atrogin-1/MAFbx 和 MuRF-1 的表达显著增加。此外，与对照组相比，纤维直径、肌球蛋白重链（MHC）I 含量显著降低，而胶原蛋白含量和肌球蛋白重链 IIa 增加。Met 治疗组与 HFD 组相比，测量参数显著降低。它还使基因表达、形态计量测量和 MHC 组成恢复正常。
本研究首次提供证据表明，Met 可改善高脂肪饮食诱导肥胖引起的肌肉萎缩，这种作用可能部分归因于 PGC-1α-FoxO3 途径的调节。
