The effects of apelin treatment on skeletal muscle mitochondrial content.
Adipose tissue is recognized as a key player in the regulation of whole body metabolism. Apelin, is a recently identified adipokine that when given to mice results in increases in skeletal muscle uncoupling protein 3 (UCP3) content. Similarly, acute apelin treatment has been shown to increase the activity of 5'-AMP-activated protein kinase (AMPK), a reputed mediator of skeletal muscle mitochondrial biogenesis. Given these findings, we sought to determine the effects of apelin on skeletal muscle mitochondrial content. Male Wistar rats were given daily intraperitoneal injections of apelin-13 (100 nmol/kg) for 2 wk. We made the novel observation that the activities of citrate synthase, cytochrome c oxidase, and beta-hydroxyacyl coA dehydrogenase (betaHAD) were increased in triceps but not heart and soleus muscles from apelin-treated rats. When confirming these results we found that both nuclear and mitochondrial-encoded subunits of the respiratory chain were increased in triceps from apelin-treated rats. Similarly, apelin treatment increased the protein content of components of the mitochondrial import and assembly pathway. The increases in mitochondrial marker proteins were associated with increases in proliferator-activated receptor-gamma coactivator-1 (PGC-1beta) but not PGC-1alpha or Pgc-1-related co-activator (PRC) mRNA expression. Chronic and acute apelin treatment did not increase the protein content and/or phosphorylation status of AMPK and its downstream substrate acetyl-CoA carboxylase. These findings are the first to demonstrate that apelin treatment can induce skeletal muscle mitochondrial content. Given the lack of an effect of apelin on AMPK signaling and PGC-1alpha mRNA expression, these results suggest that apelin increases skeletal muscle mitochondrial content through a mechanism that is distinct from that of more robust physiological stressors.
Frier
Bruce C
BC
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada T6G 2E1.
Williams
Deon B
DB
Wright
David C
DC
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000818:Animals; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D007274:Injections, Intraperitoneal; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000201:enzymology; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics; D015854:Up-Regulation
D036341:Intercellular Signaling Peptides and Proteins; D033681:Mitochondrial Membrane Transport Proteins; D018832:Molecular Chaperones; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C495199:apelin-13 peptide; D015094:3-Hydroxyacyl CoA Dehydrogenases; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase