Role and mechanism of hepatic complement factor D in regulating lipid metabolism in adipose tissue via the C5aR-AKT pathway
10.3760/cma.j.cn311282-20250418-00201
- VernacularTitle:肝脏补体因子D经C5aR-AKT通路调控脂肪组织脂代谢的作用与机制
- Author:
Yuren WANG
1
;
Hongting ZHENG
1
;
Yi ZHENG
1
;
Xin XIONG
1
Author Information
1. 陆军军医大学第二附属医院内分泌科，重庆 400037
- Publication Type:Journal Article
- Keywords:
Complement factor D;
Obesity;
Inter-organ communication;
Lipid metabolism
- From:
Chinese Journal of Endocrinology and Metabolism
2025;41(7):570-577
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the regulatory role and underlying mechanism of hepatic complement factor D(CFD) in obesity and adipose tissue metabolic disorders in high-fat diet(HFD)-induced obese mice.Methods:C57BL/6J mice were fed a HFD to induce obesity and subjected to tail vein or targeted virus injections to establish tissue-specific CFD overexpression or knockdown models. HE staining of adipose tissue was performed to evaluate adipocyte size and number. Immunohistochemical staining was used to evaluate uncoupling protein 1(UCP1) protein expression. qPCR and Western blot were conducted to detect the expression of genes related to lipid synthesis, thermogenesis, and downstream signaling pathway proteins in adipose tissue. In vitro, differentiated 3T3-L1 cells and primary stromal vascular fractions(SVF) from brown adipose tissue were treated with recombinant CFD protein combined with pathway inhibitors to verify the regulatory mechanism.Results:Liver-specific overexpression of CFD in mice led to increased adipose tissue mass ratio and aggravated insulin resistance under HFD conditions, accompanied by more severe fat accumulation and decreased energy expenditure compared with control mice. Conversely, liver-specific knockdown of CFD improved these metabolic abnormalities. Mechanistically, CFD exerted its metabolic regulatory effects by activating the C5aR-AKT signaling pathway in adipocytes. Furthermore, targeted knockdown of C5aR in adipose tissue attenuated the adverse metabolic effects induced by hepatic CFD overexpression.Conclusion:Hepatic CFD plays a critical role in the development of obesity and related metabolic disorders. These findings provide a potential novel therapeutic target for the management of obesity-associated metabolic diseases.
