Chronic AMP-activated protein kinase activation and a high-fat diet have an additive effect on mitochondria in rat skeletal muscle.
Factors that stimulate mitochondrial biogenesis in skeletal muscle include AMP-activated protein kinase (AMPK), calcium, and circulating free fatty acids (FFAs). Chronic treatment with either 5-aminoimidazole-4-carboxamide riboside (AICAR), a chemical activator of AMPK, or increasing circulating FFAs with a high-fat diet increases mitochondria in rat skeletal muscle. The purpose of this study was to determine whether the combination of chronic chemical activation of AMPK and high-fat feeding would have an additive effect on skeletal muscle mitochondria levels. We treated Wistar male rats with a high-fat diet (HF), AICAR injections (AICAR), or a high-fat diet and AICAR injections (HF + AICAR) for 6 wk. At the end of the treatment period, markers of mitochondrial content were examined in white quadriceps, red quadriceps, and soleus muscles, predominantly composed of unique muscle-fiber types. In white quadriceps, there was a cumulative effect of treatments on long-chain acyl-CoA dehydrogenase, cytochrome c, and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) protein, as well as on citrate synthase and beta-hydroxyacyl-CoA dehydrogenase (beta-HAD) activity. In contrast, no additive effect was noted in the soleus, and in the red quadriceps only beta-HAD activity increased additively. The additive increase of mitochondrial markers observed in the white quadriceps may be explained by a combined effect of two separate mechanisms: high-fat diet-induced posttranscriptional increase in PGC-1alpha protein and AMPK-mediated increase in PGC-1alpha protein via a transcriptional mechanism. These data show that chronic chemical activation of AMPK and a high-fat diet have a muscle type specific additive effect on markers of fatty acid oxidation, the citric acid cycle, the electron transport chain, and transcriptional regulation.
Department of Physiology and Developmental Biology, Birgham Young University, Provo, UT 84602, USA.
Natasha
N
Fillmore
Daniel L
DL
Jacobs
David B
DB
Mills
William W
WW
Winder
Chad R
CR
Hancock
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002952:Citric Acid Cycle / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism*; D004579:Electron Transport; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D008297:Male; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000201:enzymology; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000201:enzymology; D018657:Muscle Fibers, Slow-Twitch / Q000187:drug effects / Q000201:enzymology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology; D047495:PPAR gamma / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D052097:Quadriceps Muscle / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D012265:Ribonucleotides / Q000494:pharmacology*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D004041:Dietary Fats; D020536:Enzyme Activators; D005230:Fatty Acids, Nonesterified; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012265:Ribonucleotides; D014157:Transcription Factors; D000620:Aminoimidazole Carboxamide; D045304:Cytochromes c; D015094:3-Hydroxyacyl CoA Dehydrogenases; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide