PT  - JOURNAL ARTICLE
AU  - María Bové
AU  - Fermi Monto
AU  - Paloma Guillem-Llobat
AU  - M Dolores Ivorra
AU  - M Antonia Noguera
AU  - Andrea Zambrano
AU  - Ma Salome Sirerol-Piquer
AU  - Ana Cristina Requena
AU  - Mauricio García-Alonso
AU  - Teresa Tejerina
AU  - José T. Real
AU  - Isabel Fariñas
AU  - Pilar D’Ocon
TI  - NT3/TrkC pathway modulates the expression of UCP-1 and adipocyte size in human and murine adipose tissue
AID  - 10.1101/2020.07.24.216374
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.07.24.216374
4099  - http://biorxiv.org/content/early/2020/07/25/2020.07.24.216374.short
4100  - http://biorxiv.org/content/early/2020/07/25/2020.07.24.216374.full
AB  - NT3, through activation of its tropomyosin-related kinase receptor C (TrkC), modulates neuronal survival and neural stem cell differentiation. It is widely distributed in peripheral tissues (specially vessels and pancreas) and this ubiquitous pattern suggests a role for NT3, outside the nervous system and related to metabolic functions. The presence of the NT3/TrkC pathway in the adipose tissue (AT) has never been investigated. Present work studies in human and murine adipose tissue (AT) the presence of elements of the NT3/TrkC pathway and its role on lipolysis and adipocyte differentiation. qRT-PCR and immunoblot indicate that NT3 was present in human retroperitoneal AT and decreases with age. NT3 was also present in rat isolated adipocytes and retroperitoneal, interscapular, perivascular and perirenal AT. Histological analysis evidences that NT3 was mainly present in vessels irrigating AT close associated to sympathetic fibers. Similar mRNA levels of TrkC and β-adrenoceptors were found in all ATs assayed and in isolated adipocytes. NT3, through TrkC activation, exert a mild effect in lipolysis. Addition of NT3 during the differentiation process of human pre-adipocytes resulted in smaller adipocytes and increased uncoupling protein-1 (UCP-1) without changes in β-adrenoceptors. Similarly, transgenic mice with reduced expression of NT3 (Ntf3 knock-in lacZ reporter mice) or lacking endothelial NT3 expression (Ntf3flox1/flox2;Tie2-Cre+/0) displayed enlarged white and brown adipocytes and lower UCP-1 expression.Conclusions NT3, mainly released by blood vessels, activates TrkC and regulates adipocyte differentiation and browning. Disruption of NT3/TrkC signaling conducts to hypertrophied white and brown adipocytes with reduced expression of the thermogenesis marker UCP-1Competing Interest StatementThe authors have declared no competing interest.