| Autor: |
Virginie Vauthier, Clara Roujeau, Patty Chen, Chamsy Sarkis, Stéphanie Migrenne, Toru Hosoi, Koichiro Ozawa, Yves Rouillé, Marc Foretz, Jacques Mallet, Jean-Marie Launay, Christophe Magnan, Ralf Jockers, Julie Dam |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
|
| Zdroj: |
Molecular Metabolism, Vol 6, Iss 1, Pp 159-172 (2017) |
| Druh dokumentu: |
article |
| ISSN: |
2212-8778 |
| DOI: |
10.1016/j.molmet.2016.10.009 |
| Popis: |
The hypothalamic arcuate nucleus (ARC) is a major integration center for energy and glucose homeostasis that responds to leptin. Resistance to leptin in the ARC is an important component of the development of obesity and type 2 diabetes. Recently, we showed that Endospanin1 (Endo1) is a negative regulator of the leptin receptor (OBR) that interacts with OBR and retains the receptor inside the cell, leading to a decreased activation of the anorectic STAT3 pathway. Endo1 is up-regulated in the ARC of high fat diet (HFD)-fed mice, and its silencing in the ARC of lean and obese mice prevents and reverses the development of obesity. Objective: Herein we investigated whether decreased Endo1 expression in the hypothalamic ARC, associated with reduced obesity, could also ameliorate glucose homeostasis accordingly. Methods: We studied glucose homeostasis in lean or obese mice silenced for Endo1 in the ARC via stereotactic injection of shRNA-expressing lentiviral vectors. Results: We observed that despite being leaner, Endo1-silenced mice showed impaired glucose homeostasis on HFD. Mechanistically, we show that Endo1 interacts with p85, the regulatory subunit of PI3K, and mediates leptin-induced PI3K activation. Conclusions: Our results thus define Endo1 as an important hypothalamic integrator of leptin signaling, and its silencing differentially regulates the OBR-dependent functions. Keywords: Leptin receptor, OB-RGRP/Endospanin1, Insulin, Obesity, Diabetes |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
