Polyunsaturated fatty acids do not activate AMP-activated protein kinase in mouse tissues.
Stearoyl-CoA desaturase 1 (SCD1) deficiency partitions fatty acids away from lipid synthesis towards fatty acid oxidation in liver and skeletal muscle in part due to activation of AMP-activated protein kinase (AMPK) pathway. The mechanism of AMPK activation by SCD1 mutation is unknown, however since SCD1-/- animals have increased relative amounts of polyunsaturated fatty acids (PUFA), we hypothesized that the increased levels of PUFA might be responsible for the activation of AMPK in SCD1 deficient mice. Therefore, the present study was undertaken to analyze the effect of PUFA on AMPK in liver, skeletal muscle, and heart. We fed mice ad libitum for 14 days with diet supplemented with fish oil (5% fat). As expected, fish oil supplementation significantly increased n-3 PUFA content in each of the analyzed tissues. Hepatic mRNA levels of fatty acid synthase and acyl-CoA oxidase decreased by 92% and increased by 60%, respectively, consistent with known PUFA effects. However, after 14 days of PUFA feeding, we did not find any changes in AMPK phosphorylation and protein content in mouse liver, skeletal muscle, and heart. The data suggest that PUFA are not involved in AMPK activation in mouse tissues and that the increased activity of AMPK in SCD1-/- mice is probably PUFA-independent.
Dobrzyn
Agnieszka
A
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Dobrzyn
Pawel
P
Miyazaki
Makoto
M
Ntambi
James M
JM
D055372:AMP-Activated Protein Kinases; D042962:Acyl-CoA Oxidase / Q000235:genetics; D000818:Animals; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D064429:Fatty Acid Synthases / Q000235:genetics; D005231:Fatty Acids, Unsaturated / Q000378:metabolism / Q000494:pharmacology*; D005395:Fish Oils / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009097:Multienzyme Complexes / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase / Q000172:deficiency / Q000235:genetics
D004042:Dietary Fats, Unsaturated; D005231:Fatty Acids, Unsaturated; D005395:Fish Oils; D009097:Multienzyme Complexes; D012333:RNA, Messenger; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase; D042962:Acyl-CoA Oxidase; D064429:Fatty Acid Synthases; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases