Recent research has pinpointed a liver-specific receptor known as GPR110 as a crucial factor in understanding sex-related differences in metabolic dysfunction-associated steatohepatitis (MASH). This finding sheds light on why the severity and outcomes of the disease can vary between women and men. MASH, along with its inflammatory variant, is a significant cause of chronic liver disease globally. While both conditions are more prevalent in individuals dealing with obesity and metabolic syndrome, studies indicate that the evolution of the disease and the risk of fibrosis may differ by sex. However, the underlying biological mechanisms have not been well understood until now.
The study examined the role of GPR110, a G-protein-coupled receptor found in hepatocytes, using diet-induced models of liver disease in mice. It specifically investigated how the absence of GPR110 in hepatocytes impacted liver inflammation, fibrosis, and metabolic pathways in both male and female subjects. Additionally, genetic association analyses explored connections between variations in the GPR110 gene and liver disease risk in humans.
Key results from animal models showed that removing GPR110 from female mice offered protection against MASH features, such as inflammation and fibrosis. This protective effect was not seen in male mice, indicating a distinct, sex-specific function for this receptor in the disease’s progression. Further analysis revealed that GPR110 plays a role in regulating estrogen receptor alpha signaling within liver cells. The absence of GPR110 correlated with enhanced activity of estrogen receptors in female hepatocytes, which in turn was linked to diminished liver injury and fibrotic response. These insights suggest that GPR110 regulates hormone-dependent pathways in the liver.
Furthermore, the researchers discovered a genetic variant in the GPR110 gene that was associated with a higher incidence of metabolic liver disease among women. This discovery reinforces the clinical relevance of their experimental findings and suggests that pathways mediated by GPR110 might contribute to sex-specific susceptibility to the disease in humans.
The implications of this study emphasize the need to consider biological sex as a significant factor in understanding liver disease mechanisms and in developing new therapies. Targeting GPR110 or related signaling pathways could pave the way for personalized treatment strategies, especially for women affected by metabolic liver disease. Additional research is necessary to determine whether these mechanisms also function in human liver tissue and to assess if adjusting GPR110 can effectively improve outcomes for patients with MASH.
The study was conducted by Yang F et al. and is detailed in their publication, “Hepatic GPR110 contributes to sex disparity in the development of metabolic dysfunction-associated steatohepatitis through estrogen receptor alpha-dependent signaling,” which can be accessed for further reference.
Original Source: https://www.emjreviews.com/hepatology/news/liver-gpr110-linked-to-sex-differences-in-mash-progression/
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Publish Date: 2026-01-16 21:32:00
