title: Interactions between the consumption of a high-fat diet and fasting in the regulation of fatty acid oxidation enzyme gene expression: an evaluation of potential mechanisms.
abstract: The consumption of high-fat diets (HFDs) and fasting are known to increase the expression of enzymes involved in fatty acid oxidation (FAO). However, it has been reported that the ability of physiological stressors to induce enzymes of FAO in skeletal muscle is blunted with obesity. In this regard, we sought to explore the effects and potential mechanisms of an HFD on the expression of FAO enzymes in the fed and fasted state. The consumption of an HFD increased the mRNA expression or protein content of medium-chain acyl-CoA dehydrogenase (MCAD), uncoupling protein-3 (UCP3), and pyruvate dehydrogenase kinase 4 (PDK4) in the fed state. Fasting increased the mRNA expression of PDK4, MCAD, and UCP-3, and the protein content of UCP-3 in chow but not HFD rats. HFDs did not increase carnitine palmitoyl transfer-1 (CPT-1) mRNA levels in the fed state and the effects of fasting were markedly reduced compared with chow-fed rats. The expression of peroxisome-proliferator-activated receptor-γ coactivator-1β (PGC-1β) was increased in muscle from HFD rats in the fed state, while PGC-1-related coactivator (PRC) was increased with fasting in chow-fed but not HFD rats. Plasma fatty acid levels were elevated in the fed state from HFD rats but not increased further with fasting, whereas fasting increased plasma fatty acids in chow-fed animals. Fasting-mediated increases in plasma epinephrine, and the activation of PKA and AMPK in skeletal muscle were similar between chow and HFD rats. p38 MAPK phosphorylation was increased with fasting in chow-fed but not HFD rats. Our findings suggest that a blunted effect of fasting on the induction of PDK4, MCAD, and UCP3 in skeletal muscle from HFD rats is likely a result of already elevated levels of these enzymes, the induction of which is associated with increases in plasma fatty acid and PGC-1β. On the other hand, a blunted induction of PRC and CPT-1 mRNA may be explained by decreases in p38 MAPK signaling.
authors.affiliation: Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Frier
authors.forename: René L
authors.initials: RL
authors.lastname: Jacobs
authors.forename: David C
authors.initials: DC
authors.lastname: Wright
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000235:genetics* / Q000378:metabolism; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000102:Acetyl-CoA C-Acyltransferase / Q000235:genetics* / Q000378:metabolism; D042964:Acyl-CoA Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D019748:Carbon-Carbon Double Bond Isomerases / Q000235:genetics* / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D004746:Enoyl-CoA Hydratase / Q000235:genetics* / Q000378:metabolism; D004837:Epinephrine / Q000097:blood; D005215:Fasting / Q000097:blood / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D007328:Insulin / Q000097:blood; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008297:Male; D008931:Mitochondria, Muscle / Q000201:enzymology* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D016601:RNA-Binding Proteins / Q000235:genetics; D019998:Racemases and Epimerases / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism; D000071247:Uncoupling Protein 3; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000631440:Pdk4 protein, rat; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D016601:RNA-Binding Proteins; D018343:Receptors, Adrenergic, beta-2; D014157:Transcription Factors; D014280:Triglycerides; C000604394:Ucp3 protein, rat; D000071247:Uncoupling Protein 3; C038784:fatty acid oxidation complex; D015094:3-Hydroxyacyl CoA Dehydrogenases; D042964:Acyl-CoA Dehydrogenase; D000102:Acetyl-CoA C-Acyltransferase; D002334:Carnitine O-Palmitoyltransferase; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; D004746:Enoyl-CoA Hydratase; D019998:Racemases and Epimerases; D019748:Carbon-Carbon Double Bond Isomerases; D004837:Epinephrine