Lack of Adipocyte-Fndc5/Irisin Expression and Secretion Reduces Thermogenesis and Enhances Adipogenesis

Autor: Manuel Collado, Diego Pérez-Sotelo, Arturo Roca-Rivada, Ivan Baamonde, María Pardo, Javier Baltar, Ana I. Castro, Felipe F. Casanueva, Eduardo Domínguez
Přispěvatelé: Universidade de Santiago de Compostela. Departamento de Psiquiatría, Radioloxía, Saúde Pública, Enfermaría e Medicina
Rok vydání: 2017
Předmět:
Zdroj: Scientific Reports
Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
instname
Scientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
ISSN: 2045-2322
DOI: 10.1038/s41598-017-16602-z
Popis: Irisin is a browning-stimulating molecule secreted from the fibronectin type III domain containing 5 precursor (FNDC5) by muscle tissue upon exercise stimulation. Despite its beneficial role, there is an unmet and clamorous need to discern many essential aspects of this protein and its mechanism of action not only as a myokine but also as an adipokine. Here we contribute to address this topic by revealing the nature and role of FNDC5/irisin in adipose tissue. First, we show that FNDC5/irisin expression and secretion are induced by adipocyte differentiation and confirm its over-secretion by human obese visceral (VAT) and subcutaneous (SAT) adipose tissues. Second, we show how secreted factors from human obese VAT and SAT decrease PGC1α, FNDC5 and UCP1 gene expression on differentiating adipocytes; this effect over UCP1 is blunted by blocking irisin in obese secretomes. Finally, by stable gene silencing FNDC5 we reveal that FNDC5-KO adipocytes show reduced UCP1 expression and enhanced adipogenesis. This work was supported by Instituto de Salud Carlos III-FEDER (grant numbers PI13/01915-PI16/01212). Centro de Investigación Biomedica en Red Fisiopatología de la Obesidad y Nutrición is an ISCIII iniciative. D.P-S is funded by the Health Research Institute of Santiago (IDIS) and M.P is a Miguel Servet II Fellow (Instituto de Salud Carlos III/SERGAS) SI
Databáze: OpenAIRE