Document Detail


A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis.
MedLine Citation:
PMID:  22237023     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Pontus Boström; Jun Wu; Mark P Jedrychowski; Anisha Korde; Li Ye; James C Lo; Kyle A Rasbach; Elisabeth Almer Boström; Jang Hyun Choi; Jonathan Z Long; Shingo Kajimura; Maria Cristina Zingaretti; Birgitte F Vind; Hua Tu; Saverio Cinti; Kurt Højlund; Steven P Gygi; Bruce M Spiegelman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-01-11
Journal Detail:
Title:  Nature     Volume:  481     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-27     Completed Date:  2012-03-02     Revised Date:  2012-04-25    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  463-8     Citation Subset:  IM    
Affiliation:
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Adipocytes / cytology,  drug effects,  metabolism
Adipose Tissue, Brown / cytology*,  drug effects,  metabolism
Adipose Tissue, White / cytology*,  drug effects,  metabolism
Animals
Cell Respiration / drug effects
Cells, Cultured
Culture Media, Conditioned / pharmacology
Energy Metabolism / drug effects,  genetics,  physiology
Exercise / physiology
Gene Expression Regulation / drug effects,  genetics
Hormones / metabolism,  secretion
Humans
Insulin Resistance / physiology
Intracellular Signaling Peptides and Proteins / genetics,  metabolism
Ion Channels / metabolism
Mice
Mice, Inbred BALB C
Mice, Transgenic
Mitochondrial Proteins / metabolism
Models, Animal
Muscle Cells / metabolism
Obesity / blood,  chemically induced,  prevention & control
Physical Conditioning, Animal / physiology
Plasma / chemistry
Subcutaneous Fat / cytology,  drug effects,  metabolism
Thermogenesis* / drug effects,  genetics
Trans-Activators / deficiency,  genetics,  metabolism*,  secretion
Grant Support
ID/Acronym/Agency:
DK31405/DK/NIDDK NIH HHS; DK54477/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Culture Media, Conditioned; 0/Hormones; 0/Intracellular Signaling Peptides and Proteins; 0/Ion Channels; 0/Mitochondrial Proteins; 0/Ppargc1a protein, mouse; 0/Trans-Activators; 0/mitochondrial uncoupling protein
Comments/Corrections
Comment In:
Cell Metab. 2012 Mar 7;15(3):277-8   [PMID:  22405065 ]
Nat Rev Endocrinol. 2012 Apr;8(4):195   [PMID:  22290362 ]
Nat Rev Drug Discov. 2012 Mar;11(3):189   [PMID:  22338642 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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