Prolactin improves hepatic steatosis via CD36 pathway

Area of Science:

• Endocrinology
• Hepatology
• Metabolic Syndrome

Background:

• Prolactin (PRL) is a hormone with known metabolic effects, but its role in hepatic steatosis and lipid metabolism remains largely unexplored.
• Non-alcoholic fatty liver disease (NAFLD) is a growing health concern with complex underlying mechanisms.

Purpose of the Study:

• To investigate the association between prolactin levels and the development of non-alcoholic fatty liver disease (NAFLD).
• To elucidate the role of the prolactin receptor (PRLR) and its signaling pathways in hepatic lipid metabolism.

Main Methods:

• Serum PRL levels were measured in 456 NAFLD patients and 403 controls.
• Hepatic gene expression of PRLR and CD36 was analyzed in liver biopsies and HepG2 cells.
• In vitro experiments assessed the impact of PRLR modulation and CD36 on lipid metabolism in fatty acid-treated HepG2 cells.

Main Results:

• Lower circulating PRL levels were observed in individuals with NAFLD compared to controls.
• PRL levels correlated negatively with the severity of hepatic steatosis.
• Reduced hepatic PRLR expression in NAFLD patients was associated with increased CD36 expression.
• PRL treatment or PRLR overexpression decreased lipid accumulation in HepG2 cells, an effect dependent on PRLR and modulated by CD36.

Conclusions:

• A novel association between prolactin signaling and hepatic lipid metabolism in NAFLD is identified.
• PRL/PRLR signaling improves hepatic lipid accumulation, potentially via the CD36 pathway.
• These findings suggest a potential therapeutic strategy for NAFLD involving PRL and PRLR modulation.