title: The relationship between muscle fiber type-specific PGC-1α content and mitochondrial content varies between rodent models and humans.
abstract: PGC-1α regulates critical processes in muscle physiology, including mitochondrial biogenesis, lipid metabolism and angiogenesis. Furthermore, PGC-1α was suggested as an important regulator of fiber type determination. However, whether a muscle fiber type-specific PGC-1α content exists, whether PGC-1α content relates to basal levels of mitochondrial content, and whether such relationships are preserved between humans and classically used rodent models are all questions that have been either poorly addressed or never investigated. To address these issues, we investigated the fiber type-specific content of PGC-1α and its relationship to basal mitochondrial content in mouse, rat and human muscles using in situ immunolabeling and histochemical methods on muscle serial cross-sections. Whereas type IIa fibers exhibited the highest PGC-1α in all three species, other fiber types displayed a hierarchy of type IIx>I>IIb in mouse, type I = IIx> IIb in rat, and type IIx>I in human. In terms of mitochondrial content, we observed a hierarchy of IIa>IIx>I>IIb in mouse, IIa >I>IIx> IIb in rat, and I>IIa> IIx in human skeletal muscle. We also found in rat skeletal muscle that type I fibers displayed the highest capillarization followed by type IIa >IIx>IIb. Finally, we found in human skeletal muscle that type I fibers display the highest lipid content, followed by type IIa>IIx. Altogether, our results reveal that (i) the fiber type-specific PGC-1α and mitochondrial contents were only matched in mouse, (ii) the patterns of PGC-1α and mitochondrial contents observed in mice and rats do not correspond to that seen in humans in several respects, and (iii) the classical phenotypes thought to be regulated by PGC-1α do not vary exclusively as a function of PGC-1α content in rat and human muscles.
authors.affiliation: Department of Critical Care, McGill University Health Centre and Department of Medicine, McGill University, Montréal, Québec, Canada; Département de kinanthropologie, Faculté des sciences, Université du Québec À Montréal, Montréal, Québec, Canada.
authors.forename: Gilles
authors.initials: G
authors.lastname: Gouspillou
authors.affiliation: Department of Critical Care, McGill University Health Centre and Department of Medicine, McGill University, Montréal, Québec, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sgarioto
authors.affiliation: Department of Kinesiology and Physical Education, McGill University, Montréal, Québec, Canada.
authors.forename: Brandon
authors.initials: B
authors.lastname: Norris
authors.affiliation: Département de kinanthropologie, Faculté des sciences, Université du Québec À Montréal, Montréal, Québec, Canada.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Barbat-Artigas
authors.affiliation: Département de kinanthropologie, Faculté des sciences, Université du Québec À Montréal, Montréal, Québec, Canada.
authors.forename: Mylène
authors.initials: M
authors.lastname: Aubertin-Leheudre
authors.affiliation: Division of Geriatric Medicine, McGill University Health Centre, McGill University, Montreal, Québec, Canada.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Morais
authors.affiliation: Faculty of Pharmacy, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Yan
authors.initials: Y
authors.lastname: Burelle
authors.affiliation: Department of Kinesiology and Physical Education, McGill University, Montréal, Québec, Canada.
authors.forename: Tanja
authors.initials: T
authors.lastname: Taivassalo
authors.affiliation: Department of Critical Care, McGill University Health Centre and Department of Medicine, McGill University, Montréal, Québec, Canada; Department of Kinesiology and Physical Education, McGill University, Montréal, Québec, Canada.
authors.forename: Russell T
authors.initials: RT
authors.lastname: Hepple
mesh_terms: D000818:Animals; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014157:Transcription Factors; D018995:Myosin Heavy Chains