title: Metformin suppresses lipid accumulation in skeletal muscle by promoting fatty acid oxidation.
abstract: 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.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhang
authors.forename: Peizhen
authors.initials: P
authors.lastname: Hu
authors.forename: Zengshan
authors.initials: Z
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Ye
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002460:Cell Line; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009765:Obesity; D010084:Oxidation-Reduction; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D005227:Fatty Acids; D008687:Metformin