ArticleJCI insight2024
Adipsin and adipocyte-derived C3aR1 regulate thermogenic fat in a sex-dependent fashion.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Glucose-dependent regulation of hepatic adipsin controls glucose uptake and tolerance.Molecular medicine (Cambridge, Mass.) · 2026Article
- Type 2 and type 1 diabetes have opposing effects on the systemic murine complement alternative pathway.iScience · 2026Article
- Unique Stroma of Higher-Grade Pancreatic Intraepithelial Neoplasia: Fibroblastic Cluster Formation and CD36 Downregulation.Oncology · 2026Article
- Gestational diabetes as an inter-generational cardiometabolic risk factor: spotlight on emerging exerkines.Cardiovascular diabetology · 2026Review
- Treatment of atypical hemolytic uremic syndrome and C3 glomerulopathy in mice by hepatic expression of factor D.Blood advances · 2026Article
- Cellular gatekeepers of infected wounds: the dual role of adipocytes in coordinating immunity and regeneration.Frontiers in immunology · 2026Review
- From endocrine to immune: therapeutic potential of brown adipose tissue in remodelling the cardiovascular immune microenvironment.Frontiers in immunology · 2026Review
- Beta-cell-specific C3 deficiency exacerbates metabolic dysregulation and insulin resistance in obesity.Molecular metabolism · 2026Article
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- Subcutaneous adipose tissue gene transcripts associated with progressive myosteatosis in persons with HIV.AIDS (London, England) · 2025Article
- The secret life of complement: challenges and opportunities in exploring functions of the complosome in disease.The Journal of clinical investigation · 2025Review
- Identifying KLF14 as a potential regulatory factor in liver regeneration trough transcriptomic and metabolomic.Scientific reports · 2025Article
- Article
- Obesity's systemic impact: exploring molecular and physiological links to diabetes, cardiovascular disease, and heart failure.Frontiers in endocrinology · 2025Review
- C3AR1 may aggravate diabetic nephropathy by mediating oxidative stress via ITGB2 regulation in renal tubular epithelial cells.PloS one · 2025Article
- Complement 3a Receptor 1 on Macrophages and Kupffer cells is not required for the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease.medRxiv : the preprint server for health sciences · 2024Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Thermogenesis in beige/brown adipose tissues can be leveraged to combat metabolic disorders such as type 2 diabetes and obesity. The complement system plays pleiotropic roles in metabolic homeostasis and organismal energy balance with canonical effects on immune cells and noncanonical effects on nonimmune cells. The adipsin/C3a/C3a receptor 1 (C3aR1) pathway stimulates insulin secretion and sustains pancreatic β cell mass. However, its role in adipose thermogenesis has not been defined. Here, we show that male Adipsin/Cfd-knockout mice exhibited increased energy expenditure and white adipose tissue (WAT) browning. In addition, male adipocyte-specific C3aR1-knockout mice exhibited enhanced WAT thermogenesis and increased respiration. In stark contrast, female adipocyte-specific C3aR1-knockout mice displayed decreased brown fat thermogenesis and were cold intolerant. Female mice expressed lower levels of Adipsin in thermogenic adipocytes and adipose tissues than males. C3aR1 was also lower in female subcutaneous adipose tissue than in males. Collectively, these results reveal sexual dimorphism in the adipsin/C3a/C3aR1 axis in regulating adipose thermogenesis and defense against cold stress. Our findings establish a potentially new role of the alternative complement pathway in adaptive thermogenesis and highlight sex-specific considerations in potential therapeutic targets for metabolic diseases.
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