title: Fiber-type-specific sensitivities and phenotypic adaptations to dietary fat overload differentially impact fast- versus slow-twitch muscle contractile function in C57BL/6J mice.
abstract: High-fat diets (HFDs) have been shown to interfere with skeletal muscle energy metabolism and cause peripheral insulin resistance. However, understanding of HFD impact on skeletal muscle primary function, i.e., contractile performance, is limited. Male C57BL/6J mice were fed HFD containing lard (HFL) or palm oil (HFP), or low-fat diet (LFD) for 5weeks. Fast-twitch (FT) extensor digitorum longus (EDL) and slow-twitch (ST) soleus muscles were characterized with respect to contractile function and selected biochemical features. In FT EDL muscle, a 30%-50% increase in fatty acid (FA) content and doubling of long-chain acylcarnitine (C14-C18) content in response to HFL and HFP feeding were accompanied by increase in protein levels of peroxisome proliferator-activated receptor-γ coactivator-1α, mitochondrial oxidative phosphorylation complexes and acyl-CoA dehydrogenases involved in mitochondrial FA β-oxidation. Peak force of FT EDL twitch and tetanic contractions was unaltered, but the relaxation time (RT) of twitch contractions was 30% slower compared to LFD controls. The latter was caused by accumulation of lipid intermediates rather than changes in the expression levels of proteins involved in calcium handling. In ST soleus muscle, no evidence for lipid overload was found in any HFD group. However, particularly in HFP group, the peak force of twitch and tetanic contractions was reduced, but RT was faster than LFD controls. The latter was associated with a fast-to-slow shift in troponin T isoform expression. Taken together, these data highlight fiber-type-specific sensitivities and phenotypic adaptations to dietary lipid overload that differentially impact fast- versus slow-twitch skeletal muscle contractile function.
authors.affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, NL-5600 MB Eindhoven, The Netherlands; Netherlands Consortium for Systems Biology, PO Box 94215, NL-1090GE Amsterdam, The Netherlands; Department of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Antonius Deusinglaan 1, Building 3226, 9713 AV Groningen, The Netherlands. Electronic address: j.ciapaite@umcg.nl.
authors.forename: Jolita
authors.initials: J
authors.lastname: Ciapaite
authors.affiliation: Netherlands Consortium for Systems Biology, PO Box 94215, NL-1090GE Amsterdam, The Netherlands; Department of Human Genetics, Leiden University Medical Center, Einthovenweg 20, NL- 2333ZA Leiden, The Netherlands.
authors.forename: Sjoerd A
authors.initials: SA
authors.lastname: van den Berg
authors.affiliation: Laboratory Genetic Metabolic Diseases, Departments of Pediatrics and Clinical Chemistry, Academic Medical Center, Meibergdreef 9, NL-1105AZ Amsterdam, The Netherlands.
authors.forename: Sander M
authors.initials: SM
authors.lastname: Houten
authors.affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, NL-5600 MB Eindhoven, The Netherlands.
authors.forename: Klaas
authors.initials: K
authors.lastname: Nicolay
authors.affiliation: Netherlands Consortium for Systems Biology, PO Box 94215, NL-1090GE Amsterdam, The Netherlands; Department of Human Genetics, Leiden University Medical Center, Einthovenweg 20, NL- 2333ZA Leiden, The Netherlands.
authors.forename: Ko Willems
authors.initials: KW
authors.lastname: van Dijk
authors.affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, NL-5600 MB Eindhoven, The Netherlands; Netherlands Consortium for Systems Biology, PO Box 94215, NL-1090GE Amsterdam, The Netherlands; Department of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Antonius Deusinglaan 1, Building 3226, 9713 AV Groningen, The Netherlands.
authors.forename: Jeroen A
authors.initials: JA
authors.lastname: Jeneson
mesh_terms: D042964:Acyl-CoA Dehydrogenase / Q000378:metabolism; D052636:Allostasis; D000818:Animals; D002331:Carnitine / Q000031:analogs & derivatives / Q000378:metabolism; D018752:Diet, Fat-Restricted / Q000009:adverse effects; D059305:Diet, High-Fat / Q000009:adverse effects*; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000378:metabolism*; D009119:Muscle Contraction; D018656:Muscle Fibers, Fast-Twitch / Q000201:enzymology / Q000378:metabolism*; D018657:Muscle Fibers, Slow-Twitch / Q000201:enzymology / Q000378:metabolism*; D009126:Muscle Relaxation; D009765:Obesity / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011897:Random Allocation; D014157:Transcription Factors / Q000378:metabolism; D020107:Troponin T / Q000378:metabolism
chemical_list: D045222:Electron Transport Chain Complex Proteins; D005227:Fatty Acids; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D014157:Transcription Factors; D020107:Troponin T; C116917:acylcarnitine; D006003:Glycogen; D042964:Acyl-CoA Dehydrogenase; D002331:Carnitine
keywords: Fatty acid metabolism; Fiber type; High-fat-diet-induced obesity; Oxidative phosphorylation; Skeletal muscle function; Troponin T