RT Journal Article T1 Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance. A1 Moreno-Navarrete, José María A1 Ortega, Francisco A1 Serrano, Marta A1 Guerra, Ester A1 Pardo, Gerard A1 Tinahones, Francisco A1 Ricart, Wifredo A1 Fernández-Real, José Manuel K1 Fibronectinas K1 Tejido Adiposo K1 Células Cultivadas K1 Diabetes Mellitus Tipo 2 K1 Expresión Génica K1 Estudios de Asociación Genética K1 Resistencia a la Insulina K1 Ratones K1 Músculo Esquelético K1 Obesidad K1 Células 3T3-L1 AB CONTEXTRecently irisin (encoded by Fndc5 gene) has been reported to stimulate browning and uncoupling protein 1 expression in sc adipose tissue of mice.OBJECTIVEThe 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.DESIGN, PATIENTS, AND MAIN OUTCOME MEASUREAdipose 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.RESULTSIn 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.CONCLUSIONSDecreased 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. PB Endocrine Society SN 0021-972X YR 2013 FD 2013-04 LK http://hdl.handle.net/10668/1579 UL http://hdl.handle.net/10668/1579 LA en NO Moreno-Navarrete JM, Ortega F, Serrano M, Guerra E, Pardo G, Tinahones F, et al. Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance. J Clin Endocrinol Metab. 2013; 98(4):E769-78 NO Journal Article; Research Support, Non-U.S. Gov't; DS RISalud RD Apr 8, 2025