title: Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance.
abstract: BACKGROUND
  Recently irisin (encoded by Fndc5 gene) has been reported to stimulate browning and uncoupling protein 1 expression in sc adipose tissue of mice.
  
  
  OBJECTIVE
  The objective of the study was to investigate FNDC5 gene expression in human muscle and adipose tissue and circulating irisin according to obesity, insulin sensitivity, and type 2 diabetes.
  
  
  METHODS
  Adipose tissue FNDC5 gene expression and circulating irisin (ELISA) were analyzed in 2 different cohorts (n = 125 and n = 76); muscle FNDC5 expression was also evaluated in a subcohort of 34 subjects. In vitro studies in human preadipocytes and adipocytes and in induced browning of 3T3-L1 cells (by means of retinoblastoma 1 silencing) were also performed.
  
  
  RESULTS
  In both sc and visceral adipose tissue, FNDC5 gene expression decreased significantly in association with obesity and was positively associated with brown adipose tissue markers, lipogenic, insulin pathway-related, mitochondrial, and alternative macrophage gene markers and negatively associated with LEP, TNFα, and FSP27 (a known repressor of brown genes). Circulating irisin and irisin levels in adipose tissue were significantly associated with FNDC5 gene expression in adipose tissue. In muscle, the FNDC5 gene was 200-fold more expressed than in adipose tissue, and its expression was associated with body mass index, PGC1α, and other mitochondrial genes. In obese participants, FNDC5 gene expression in muscle was significantly decreased in association with type 2 diabetes. Interestingly, muscle FNDC5 gene expression was significantly associated with FNDC5 and UCP1 gene expression in visceral adipose tissue. In men, circulating irisin levels were negatively associated with obesity and insulin resistance. Irisin was secreted from human adipocytes into the media, and the induction of browning in 3T3-L1 cells led to increased secreted irisin levels.
  
  
  CONCLUSIONS
  Decreased circulating irisin concentration and FNDC5 gene expression in adipose tissue and muscle from obese and type 2 diabetic subjects suggests a loss of brown-like characteristics and a potential target for therapy.
authors: Department of Diabetes, Endocrinology, and Nutrition, Hospital of Girona Dr Josep Trueta, Girona, Spain.
authors: José María
authors: JM
authors: Moreno-Navarrete
authors: Francisco
authors: F
authors: Ortega
authors: Marta
authors: M
authors: Serrano
authors: Ester
authors: E
authors: Guerra
authors: Gerard
authors: G
authors: Pardo
authors: Francisco
authors: F
authors: Tinahones
authors: Wifredo
authors: W
authors: Ricart
authors: José Manuel
authors: JM
authors: Fernández-Real
mesh_terms: D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000818:Animals; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D056726:Genetic Association Studies; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics* / Q000502:physiology; D008297:Male; D051379:Mice; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: C577593:FNDC5 protein, human; D005353:Fibronectins