FATP1 mediates fatty acid-induced activation of AMPK in 3T3-L1 adipocytes.
Fatty acid transport proteins are integral membrane acyl-CoA synthetases implicated in adipocyte fatty acid influx and esterification. FATP-dependent production of AMP was evaluated using FATP4 proteoliposomes, and fatty acid-dependent activation of AMP-activated protein kinase (AMPK) was assessed in 3T3-L1 adipocytes. Insulin-stimulated fatty acid influx (palmitate or arachidonate) into cultured adipocytes resulted in an increase in the phosphorylation of AMPK and its downstream target acetyl-CoA carboxylase. Consistent with the activation of AMPK, palmitate uptake into 3T3-L1 adipocytes resulted in an increase in intracellular [AMP]/[ATP]. The fatty acid-induced increase in AMPK activation was attenuated in a cell line expressing shRNA targeting FATP1. Taken together, these results demonstrate that, in adipocytes, insulin-stimulated fatty acid influx mediated by FATP1 regulates AMPK and provides a potential regulatory mechanism for balancing de novo production of fatty acids from glucose metabolism with influx of preformed fatty acids via phosphorylation of acetyl-CoA carboxylase.
Wiczer
Brian M
BM
Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
Lobo
Sandra
S
Machen
G Luke
GL
Graves
Lee M
LM
Bernlohr
David A
DA
D041721:3T3-L1 Cells; D000091162:AMP-Activated Protein Kinase Kinases; D017667:Adipocytes / Q000201:enzymology*; D000818:Animals; D003066:Coenzyme A Ligases / Q000378:metabolism; D004789:Enzyme Activation; D050612:Fatty Acid Transport Proteins / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism* / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D010766:Phosphorylation; D011494:Protein Kinases / Q000096:biosynthesis*
D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; D007328:Insulin; C493569:Slc27a1 protein, mouse; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D003066:Coenzyme A Ligases