title: Impaired exercise tolerance, mitochondrial biogenesis, and muscle fiber maintenance in miR-133a-deficient mice.
abstract: Exercise promotes multiple beneficial effects on muscle function, including induction of mitochondrial biogenesis. miR-133a is a muscle-enriched microRNA that regulates muscle development and function. The role of miR-133a in exercise tolerance has not been fully elucidated. In the current study, mice that were deficient in miR-133a demonstrated low maximal exercise capacity and low resting metabolic rate. Transcription of the mitochondrial biogenesis regulators peroxisome proliferator-activated receptor-γ coactivator 1-α, peroxisome proliferator-activated receptor-γ coactivator 1-β, nuclear respiratory factor-1, and transcription factor A, mitochondrial were lower in miR-133a-deficient muscle, which was consistent with lower mitochondrial mass and impaired exercise capacity. Six weeks of endurance exercise training increased the transcriptional level of miR-133a and stimulated mitochondrial biogenesis in wild-type mice, but failed to improve mitochondrial function in miR-133a-deficient mice. Further mechanistic analysis showed an increase in the miR-133a potential target, IGF-1 receptor, along with hyperactivation of Akt signaling, in miR-133a-deficient mice, which was consistent with lower transcription of the mitochondrial biogenesis regulators. These findings indicate an essential role of miR-133a in skeletal muscle mitochondrial biogenesis, exercise tolerance, and response to exercise training.-Nie, Y., Sato, Y., Wang, C., Yue, F., Kuang, S., Gavin, T. P. Impaired exercise tolerance, mitochondrial biogenesis, and muscle fiber maintenance in miR-133a-deficient mice.
authors.affiliation: Department of Health and Kinesiology, Purdue University, West Lafayette, Indiana, USA.|Max E. Wastl Human Performance Laboratory, Purdue University, West Lafayette, Indiana, USA.|Department of Animal Sciences, Purdue University, West Lafayette, Indiana, USA; and.
authors.forename: Yaohui
authors.initials: Y
authors.lastname: Nie
authors.affiliation: Department of Health and Kinesiology, Purdue University, West Lafayette, Indiana, USA.|Max E. Wastl Human Performance Laboratory, Purdue University, West Lafayette, Indiana, USA.|Department of United Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology, Tokyo, Japan.
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Animal Sciences, Purdue University, West Lafayette, Indiana, USA; and.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Animal Sciences, Purdue University, West Lafayette, Indiana, USA; and.
authors.forename: Feng
authors.initials: F
authors.lastname: Yue
authors.affiliation: Department of Animal Sciences, Purdue University, West Lafayette, Indiana, USA; and skuang@purdue.edu.
authors.forename: Shihuan
authors.initials: S
authors.lastname: Kuang
authors.affiliation: Department of Health and Kinesiology, Purdue University, West Lafayette, Indiana, USA; gavin1@purdue.edu.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Gavin
mesh_terms: D000818:Animals; D017079:Exercise Tolerance / Q000502:physiology*; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D008928:Mitochondria / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D001678:Organelle Biogenesis; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000379:methods; D010807:Physical Endurance / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D035683:MicroRNAs; C517732:Mirn133 microRNA, mouse; D047492:Peroxisome Proliferator-Activated Receptors; D014157:Transcription Factors
keywords: Igf1R-Akt signaling; exercise resistance; miRNA; mitochondrial function; skeletal muscle adaptation