Metformin Suppresses Lipid Accumulation in Skeletal Muscle by Promoting Fatty Acid Oxidation
Metformin Suppresses Lipid Accumulation in Skeletal Muscle by Promoting Fatty Acid Oxidation
复制标题
二甲双胍通过促进脂肪酸氧化来抑制骨骼肌中的脂质积累。
DOI：
10.7754/clin.lab.2013.130531
复制
发表时间：
2014-01-01
影响因子：
0.7
通讯作者：
Ye, Jing
中科院分区：
文献类型：
--
作者：
Wang, Chao;Liu, Fang;Ye, Jing
背景
肥胖是代谢综合征的主要危险因素，包括胰岛素抵抗（IR）、2型糖尿病（T2 DM）和心血管疾病;异位脂肪沉积在这些疾病的发展中起着关键作用。在胰岛素抵抗和/或T2 DM患者中，骨骼肌中的脂质蓄积增加;脂肪酸代谢产物的肌内蓄积被认为在代谢综合征中起关键作用。除了改善胰岛素敏感性外，抗糖尿病药物二甲双胍还可以减少骨骼肌中的脂质积聚;然而，其作用机制尚不清楚。
方法
以Ob/ob小鼠和C2 C12细胞为研究对象，探讨二甲双胍对脂滴形态和生理变化的影响。为了阐明二甲双胍调节脂肪酸代谢的机制，使用cDNA微阵列和定量实时PCR检测二甲双胍对200 μ mol/L油酸处理的C2 C12细胞转录组的影响。
结果
二甲双胍能抑制肥胖基因型小鼠体重增加，改善胰岛素敏感性，减少肌细胞内脂质沉积。在C2 C12细胞中，二甲双胍抑制脂质蓄积，刺激脂肪酸氧化，并减少甘油三酯合成。27个差异表达基因，包括12个上调和15个下调基因，涉及脂肪酸代谢。有趣的是，参与酰基辅酶A合成和脂肪酸氧化的几个基因也被上调，如Ppard，Acsbg 1，Ascl 3和Mlycd。然而，与脂解相关的几个基因下调，如Ces 1d和Cel。此外，与脂质代谢相关的几个重要基因也下调，如Fabp 4，Adipoq和Apoc 2。
结论
二甲双胍通过促进脂肪酸氧化延缓体重增加，改善胰岛素敏感性，并抑制骨骼肌中的脂质积聚。
BACKGROUND
Obesity is a major risk factor for metabolic syndrome, including insulin resistance (IR), type 2 diabetes mellitus (T2DM), and cardiovascular disease; ectopic fat deposition plays a key role in the development of these conditions. In insulin-resistant and/or T2DM patients, lipid accumulation is increased in skeletal muscle; the intramuscular accumulation of fatty acid metabolites is recognized to play a critical role in metabolic syndrome. Besides improving insulin sensitivity, the anti-diabetic drug metformin can reduce lipid accumulation in skeletal muscle; however, its mechanism of action remains unclear.
METHODS
Ob/ob mice and C2C12 cells were used to explore the effects of metformin on the morphological and physiological changes of lipid droplets. To clarify the mechanism by which metformin regulates fatty acid metabolism, a cDNA microarray and quantitative real-time PCR were used to examine the effects of metformin on the transcriptome of C2C12 cells treated with 200 micromol/L oleic acid.
RESULTS
Metformin could retard body weight gain, improve insulin sensitivity and reduce intramyocellular lipid accumulation in ob/ob mice. In C2C12 cells, metformin inhibited lipid accumulation, stimulated fatty acid oxidation, and decreased triglyceride synthesis. Twenty-seven differentially expressed genes, including 12 upregulated and 15 downregulated genes, were involved in fatty acid metabolism. Interestingly, several genes involved in acyl-CoA synthesis and fatty acid oxidation were also upregulated, such as Ppard, Acsbg1, Ascl3, and Mlycd. However, several genes related to lipolysis were downregulated, such as Ces1d and Cel. Moreover, several important genes related to lipid metabolism were also downregulated, such as Fabp4, Adipoq, and Apoc2.
CONCLUSIONS
Metformin retards body weight gain, improves insulin sensitivity, and suppresses lipid accumulation in skeletal muscle by promoting fatty acid oxidation.