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GPSM1 in POMC neurons impairs brown adipose tissue thermogenesis and provokes diet-induced obesity

Authors :
Mengyang Tang
Yi Zhang
Rong Zhang
Yuemei Zhang
Jiangfei Zheng
Daixi Wang
Xinyu Wang
Jing Yan
Cheng Hu
Source :
Molecular Metabolism, Vol 79, Iss , Pp 101839- (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

Objective: G-protein-signaling modulator 1 (GPSM1) has been proved the potential role in brain tissues, however, whether GPSM1 in hypothalamic nuclei, especially in POMC neurons is essential for the proper regulation of whole-body energy balance remains unknown. The aim of our current study was to explore the role of GPSM1 in POMC neurons in metabolic homeostasis. Methods: We generated POMC neuron specific GPSM1 deficiency mice and subjected them to a High Fat Diet to monitor metabolic phenotypes in vivo. By using various molecular, biochemical, immunofluorescent, immunohistochemical analyses, and cell culture studies to reveal the pathophysiological role of GPSM1 in POMC neurons and elucidate the underlying mechanisms of GPSM1 regulating POMC neurons activity. Results: We demonstrated that mice lacking GPSM1 in POMC neurons were protected against diet-induced obesity, glucose dysregulation, insulin resistance, and hepatic steatosis. Mechanistically, GPSM1 deficiency in POMC neurons induced enhanced autophagy and improved leptin sensitivity through PI3K/AKT/mTOR signaling, thereby increasing POMC expression and α-MSH production, and concurrently enhancing sympathetic innervation and activity, thus resulting in decreased food intake and increased brown adipose tissue thermogenesis. Conclusions: Our findings identify a novel function of GPSM1 expressed in POMC neurons in the regulation of whole-body energy balance and metabolic homeostasis by regulating autophagy and leptin sensitivity, which suggests that GPSM1 in the POMC neurons could be a promising therapeutic target to combat obesity and obesity-related metabolic disorders.

Details

Language :
English
ISSN :
22128778
Volume :
79
Issue :
101839-
Database :
Directory of Open Access Journals
Journal :
Molecular Metabolism
Publication Type :
Academic Journal
Accession number :
edsdoj.06c803feb644c8ea6c7269eab0bcdcc
Document Type :
article
Full Text :
https://doi.org/10.1016/j.molmet.2023.101839