Netrin-1 disrupt high-fat-diet-induced adipogenesis via the PPARγ and Wnt/β-catenin signaling pathways
Year: 2026
Type: article
Abstract: The present study reports a detrimental role of adipose-derived Netrin-1 in adipose remodeling. Following an 8-week high-fat feeding period of male transgenic mice lacking adipose Netrin-1 expression ( Ntn1 AKO ), improved metabolic parameters were observed, accompanied by systemic weight gain and increased inguinal white adipose tissue (WAT) mass. The Ntn1 AKO preadipocytes exhibit increased cell proliferation with decreased collagen deposition. WAT Netrin-1 overexpression using adeno-associated virus (with an aP2 promoter) results in impaired glucose tolerance in both high fat and normal chow-fed mice. Netrin-1 overexpression attenuates adipogenesis via inhibition of the PPARγ activity and activation of the Wnt/β-catenin pathway. Moreover, Netrin-1 is directly responsive to the hypoxic regulator HIF-1α in both adipocytes and preadipocytes. The present study suggests that Netrin-1 disrupts adipogenesis and adipocyte function by inhibiting compensatory adipose remodeling during excessive calorie intake and may be considered a potential therapeutic target for high fat diet-induced obesity and type 2 diabetes.
Source: Communications Biology
Authors: Hang Shi, Jianghai Tang, Xuemiao Yan, Tingyu Ke, Duo Mao, Deling Kong, Chen Li
Institutions: Sun Yat-sen University, Chinese Academy of Medical Sciences & Peking Union Medical College, The First Affiliated Hospital, Sun Yat-sen University, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences, Tianjin First Center Hospital, Kunming Medical University, Nankai University, State Key Laboratory of Medicinal Chemical Biology
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,190
OpenAlex ID: W7130835429