Lipin-1 Drives Browning of White Adipocytes via Promotion of Brown Phenotype Markers

Background: Enhancing adipose tissue functionality is a promising cellular-level approach to combating obesity. White adipose tissue (WAT) can acquire beige or brown adipose tissue (BAT)-like properties, characterized by increased thermogenesis and energy dissipation. While the SIRT1-SRSF10-Lipin-1 axis has been identified in hepatocytes, where Lipin-1 regulates triglyceride metabolism, its role in adipocytes remains unclear. This study aimed to investigate the function of Lipin-1 in 3T3-L1 preadipocytes and its interaction with SIRT1, SRSF10, and PPARγ in promoting browning-like transcriptional responses. Methods: Mouse 3T3-L1 preadipocytes were treated during differentiation with either rosiglitazone (RGZ), the SIRT1 activator SRT1720, or the SIRT1 inhibitor EX527. Gene expression was assessed by real-time PCR, and protein levels were measured using the Simple Western blot system. Data were compared with untreated controls and analyzed using GraphPad Prism. Results: Lipin-1 expression was significantly upregulated by RGZ treatment, alongside increased transcription of Sirt1 and Srsf10, supporting the presence of this regulatory axis in adipocytes. Elevated Srsf10 favored the production of the Lipin-1b isoform, whereas SIRT1 inhibition reversed these effects, confirming its upstream role. Pathway activation further enhanced the expression of browning markers, including Ucp1, Pgc1a, PRDM16, and CIDEA. Conclusions: These findings demonstrate that Lipin-1 interacts with the SIRT1-PPARγ-SRSF10 axis in adipocytes and contributes to the acquisition of beige/brown-like characteristics in WAT. This regulatory pathway may represent a potential target for improving lipid metabolism and metabolic health.