A role for AMPK in the inhibition of glucose-6-phosphate dehydrogenase by polyunsaturated fatty acids.
Both polyunsaturated fatty acids and AMPK promote energy partitioning away from energy consuming processes, such as fatty acid synthesis, towards energy generating processes, such as beta-oxidation. In this report, we demonstrate that arachidonic acid activates AMPK in primary rat hepatocytes, and that this effect is p38 MAPK-dependent. Activation of AMPK mimics the inhibition by arachidonic acid of the insulin-mediated induction of G6PD. Similar to intracellular signaling by arachidonic acid, AMPK decreases insulin signal transduction, increasing Ser(307) phosphorylation of IRS-1 and a subsequent decrease in AKT phosphorylation. Overexpression of dominant-negative AMPK abolishes the effect of arachidonic acid on G6PD expression. These data suggest a role for AMPK in the inhibition of G6PD by polyunsaturated fatty acids.
Kohan
Alison B
AB
Department of Biochemistry, West Virginia University, Morgantown, 26506, USA.
Talukdar
Indrani
I
Walsh
Callee M
CM
Salati
Lisa M
LM
D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D016718:Arachidonic Acid / Q000096:biosynthesis / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis* / Q000494:pharmacology; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology*; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction
D005231:Fatty Acids, Unsaturated; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D016718:Arachidonic Acid; D012694:Serine; D005954:Glucosephosphate Dehydrogenase; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases