Updating the effects of fatty acids on skeletal muscle.
In this review we updated the fatty acid (FA) effects on skeletal muscle metabolism. Abnormal FA availability induces insulin resistance and accounts for several of its symptoms and complications. Efforts to understand the pathogenesis of insulin resistance are focused on disordered lipid metabolism and consequently its effect on insulin signaling pathway. We reviewed herein the FA effects on metabolism, signaling, regulation of gene expression and oxidative stress in insulin resistance. The elevated IMTG content has been associated with increased intracellular content of diacylglycerol (DAG), ceramides and long-chain acyl-coenzyme A (LCA-CoA). This condition has been shown to promote insulin resistance by interfering with phosphorylation of proteins of the insulin pathway including insulin receptor substrate-1/2 (IRS), phosphatidylinositol-3-kinase, (PI3-kinase) and protein kinase C. Although the molecular mechanism is not completely understood, elevated reactive oxygen (ROS) and nitrogen species (RNS) are involved in this process. Elevated ROS/RNS activates nuclear factor-kappaB (NFkB), which promotes the transcription of proinflammatory tumoral necrosis factor alpha (TNFalpha), decreasing the insulin response. Therefore, oxidative stress induced by elevated FA availability may constitute one of the major causes of insulin resistance in skeletal muscle.
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil. lrs@icb.usp.br
Leonardo R
LR
Silveira
Jarlei
J
Fiamoncini
Sandro M
SM
Hirabara
Joaquim
J
Procópio
Tavane D
TD
Cambiaghi
Carlos Hermano J
CH
Pinheiro
Lúcia R
LR
Lopes
Rui
R
Curi
D000818:Animals; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*
D005227:Fatty Acids