title: A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis.
abstract: Exercise benefits a variety of organ systems in mammals, and some of the best-recognized effects of exercise on muscle are mediated by the transcriptional co-activator PPAR-γ co-activator-1 α (PGC1-α). Here we show in mouse that PGC1-α expression in muscle stimulates an increase in expression of FNDC5, a membrane protein that is cleaved and secreted as a newly identified hormone, irisin. Irisin acts on white adipose cells in culture and in vivo to stimulate UCP1 expression and a broad program of brown-fat-like development. Irisin is induced with exercise in mice and humans, and mildly increased irisin levels in the blood cause an increase in energy expenditure in mice with no changes in movement or food intake. This results in improvements in obesity and glucose homeostasis. Irisin could be therapeutic for human metabolic disease and other disorders that are improved with exercise.
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Pontus
authors.initials: P
authors.lastname: Boström
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Mark P
authors.initials: MP
authors.lastname: Jedrychowski
authors.forename: Anisha
authors.initials: A
authors.lastname: Korde
authors.forename: Li
authors.initials: L
authors.lastname: Ye
authors.forename: James C
authors.initials: JC
authors.lastname: Lo
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Rasbach
authors.forename: Elisabeth Almer
authors.initials: EA
authors.lastname: Boström
authors.forename: Jang Hyun
authors.initials: JH
authors.lastname: Choi
authors.forename: Jonathan Z
authors.initials: JZ
authors.lastname: Long
authors.forename: Shingo
authors.initials: S
authors.lastname: Kajimura
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Zingaretti
authors.forename: Birgitte F
authors.initials: BF
authors.lastname: Vind
authors.forename: Hua
authors.initials: H
authors.lastname: Tu
authors.forename: Saverio
authors.initials: S
authors.lastname: Cinti
authors.forename: Kurt
authors.initials: K
authors.lastname: Højlund
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gygi
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Spiegelman
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D052436:Adipose Tissue, White / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D019069:Cell Respiration / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D015444:Exercise / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006728:Hormones / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D024101:Mitochondrial Proteins / Q000378:metabolism; D023421:Models, Animal; D032342:Muscle Cells / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal / Q000502:physiology; D010949:Plasma / Q000737:chemistry; D050151:Subcutaneous Fat / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D022722:Thermogenesis / Q000187:drug effects / Q000235:genetics; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D000071256:Uncoupling Protein 1
chemical_list: D017077:Culture Media, Conditioned; D006728:Hormones; D047908:Intracellular Signaling Peptides and Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1