title: Irisin stimulates muscle growth-related genes and regulates adipocyte differentiation and metabolism in humans.
abstract: BACKGROUND
  Irisin is a recently identified exercise-induced myokine suggested to induce browning of white adipocytes. Deficiency of myostatin, and thus stimulation of muscle growth, has also been reported to induce irisin and its precursor FNDC5 expression in muscle and drive the browning of white adipocytes in mice, implying that irisin may be related to muscle growth in addition to its beneficial effects in adipocytes. In humans, the effect of irisin in muscle hypertrophy as well as adipocyte metabolism has not been fully investigated.
  
  
  METHODS
  Primary cultured human myocytes/adipocytes and 3T3-L1 cells were used to examine irisin-regulated gene/protein expression. Lipid accumulation, ATP content, glycolysis, lipolysis and metabolite profile were measured in control and irisin-treated (10 and 50 nM) adipocytes.
  
  
  RESULTS
  In human myocytes, FNDC5 mRNA and irisin secretion were increased during myogenic differentiation, along with PGC1α and myogenin expression. Irisin treatment significantly increased insulin-like growth factor 1 and decreased myostatin gene expression through ERK pathway. PGC1α4, a newly discovered PGC1α isoform specifically related to muscle hypertrophy, was also upregulated. In human adipocytes, irisin induced uncoupling protein 1 and consequently increased adipocyte energy expenditure, expression of metabolic enzymes and metabolite intermediates, resulting in inhibition of lipid accumulation. Irisin and FNDC5 treatment also reduced preadipocyte differentiation, suggesting an additional mechanism in suppressing fat mass.
  
  
  CONCLUSIONS
  These results suggest that irisin/FNDC5 has a pleiotropic role in muscle and improvement of adipocyte metabolism in humans.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: J Y
authors.initials: JY
authors.lastname: Huh
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: F
authors.initials: F
authors.lastname: Dincer
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Mesfum
authors.affiliation: 1] Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA [2] Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Mantzoros
mesh_terms: D041721:3T3-L1 Cells / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007333:Insulin Resistance; D051379:Mice; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D015415:Biomarkers; C577593:FNDC5 protein, human; D005353:Fibronectins; D012333:RNA, Messenger