Regulation of fatty acid uptake and metabolism in L6 skeletal muscle cells by resistin.
Resistin has been proposed as a potential link between obesity and insulin resistance. It is also well established that altered metabolism of fatty acids by skeletal muscle can lead to insulin resistance and lipotoxicity. However, little is known about the effect of resistin on long chain fatty acid uptake and metabolism in skeletal muscle. Here we show that treating rat skeletal muscle cells with recombinant resistin (50 nM, 24 h) decreased uptake of palmitate. This correlated with reduced cell surface CD36 content and lower expression of FATP1, but no change in FATP4 or CD36 expression. We also found that resistin decreased fatty acid oxidation by measuring 14CO2 production from [1-14C] oleate and an increase in intracellular lipid accumulation was detected in response to resistin. Decreased AMPK and ACC phosphorylation were observed in response to resistin while expression of ACC and AMPK isoforms was unaltered. Resistin mediated these effects without altering cell viability. In summary, our results demonstrate that chronic incubation of skeletal muscle cells with resistin decreased fatty acid uptake and metabolism via a mechanism involving decreased cell surface CD36 content, FATP1 expression and a decrease in phosphorylation of AMPK and ACC.
Palanivel
Rengasamy
R
Department of Biology, York University, Toronto, Ont., Canada M3J 1P3.
Sweeney
Gary
G
D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism; D002460:Cell Line; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D006729:Hormones, Ectopic / Q000378:metabolism*; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism*; D010084:Oxidation-Reduction; D019308:Palmitic Acid / Q000737:chemistry / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D052243:Resistin
D018955:CD36 Antigens; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; D006729:Hormones, Ectopic; D026901:Membrane Transport Proteins; D009097:Multienzyme Complexes; C499624:RETN protein, human; D052243:Resistin; C499622:Retn protein, rat; C493568:SLC27A1 protein, human; C493571:SLC27A4 protein, human; C493572:Slc27a4 protein, mouse; D019308:Palmitic Acid; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase