AMPK and ACC phosphorylation: effect of leptin, muscle fibre type and obesity.
Leptin stimulates fatty acid oxidation via the phosphorylation of AMPK (AMP-activated protein kinase) and ACC (acetyl-CoA carboxylase). Obesity is associated with resistance to the effects of leptin. We determined the action of leptin on AMPKalpha and ACCbeta phosphorylation and lipid metabolism in soleus (SOL) and extensor digitorum longus (EDL) muscles from lean and obese Wistar rats after 1 and 100 nM leptin. Both leptin doses stimulated phosphorylation of AMPKalpha and ACCbeta (P<or=0.05) only in EDL muscles from lean animals. Malonyl-CoA levels were decreased in EDL muscles from lean animals after 1 and 100 nM leptin and significantly after 100 nM leptin in obese animals (P<or=0.05). Long-chain fatty acyl-CoA concentrations were decreased in EDL muscles from both phenotypes after 100 nM leptin. AMPK activation by leptin occurred independently of energy-related metabolites. These data demonstrate that the leptin effect on AMPKalpha and ACCbeta is muscle fibre type dependent and fails in diet-induced obesity.
Janovská
A
A
Discipline of Medicine, University of Adelaide, Adelaide, SA 5005, Australia. alena.janovska@adelaide.edu.au
Hatzinikolas
G
G
Staikopoulos
V
V
McInerney
J
J
Mano
M
M
Wittert
G A
GA
D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism*; D000214:Acyl Coenzyme A / Q000378:metabolism; D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D001835:Body Weight; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism; D004789:Enzyme Activation; D005227:Fatty Acids / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008316:Malonyl Coenzyme A / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000201:enzymology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009765:Obesity / Q000201:enzymology / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000214:Acyl Coenzyme A; D004041:Dietary Fats; D005227:Fatty Acids; D007328:Insulin; D020738:Leptin; D009097:Multienzyme Complexes; D008316:Malonyl Coenzyme A; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase