GPR110 & MASH: Sex-Based Liver Disease Differences

BOSTON, January 16, 2026 – A newly identified liver receptor, GPR110, appears to be a key reason why metabolic dysfunction-associated steatohepatitis (MASH) – a severe form of fatty liver disease – progresses differently in men adn women. It’s a fascinating twist, and one that could reshape how we approach treatment for this increasingly common condition.

Why Does Liver Disease Hit Men and Women Differently?

Metabolic dysfunction-associated steatotic liver disease (MASLD) and it’s inflammatory cousin, MASH, are escalating global health concerns.

• Research pinpoints GPR110 as a potential driver of sex-specific differences in MASH progression.
• Deleting GPR110 protected female mice from developing MASH, but had no effect in males.
• A genetic variant in the GPR110 gene was linked to a higher prevalence of metabolic liver disease in women.
• Targeting GPR110 could lead to personalized treatments for MASH, notably for women.

While obesity and metabolic syndrome are risk factors for both sexes, studies have long suggested that women are less likely to develop severe forms of MASH, but when they do, the disease can progress more rapidly. Now, research published in Communications Biology sheds light on a potential description: the GPR110 receptor.

Researchers found that in male mice, GPR110 appears to *promote* the advancement of MASH. Though, in female mice, removing GPR110 had a protective effect, substantially reducing liver damage and fibrosis. This suggests GPR110 plays a distinctly different role in disease progression depending on sex.

The study revealed that GPR110 influences signaling pathways involving the oestrogen receptor alpha within liver cells. Removing GPR110 boosted activity of this receptor in female hepatocytes, leading to reduced liver damage and less fibrosis.

Essentially, GPR110 appears to regulate hormone-dependent processes within the liver, and its absence seems to unlock a protective mechanism in females.

Human Genetic Links

The research didn’t stop wiht mice. Researchers identified a specific genetic variant within the GPR110 gene that was associated with a higher incidence of metabolic liver disease in women. This finding strengthens the clinical relevance of the animal studies and suggests that GPR110-related pathways may contribute to sex-specific vulnerability to the disease in humans.

what Does This Mean for the Future of Liver Disease Treatment?

This study underscores the critical need to consider biological sex when investigating liver disease and developing new therapies. Targeting GPR110 or the signaling pathways it influences could pave the way for personalized treatment strategies, particularly for women battling metabolic liver disease.

What’s the key takeaway? Understanding the role of GPR110 could unlock more effective, tailored treatments for MASH, perhaps improving outcomes for women who are disproportionately affected by certain aspects of the disease.

Further research is essential to confirm these findings in human liver tissue and to assess the safety and efficacy of modulating GPR110 as a therapeutic target.

Reference

Yang F et al. Hepatic GPR110 contributes to sex disparity in the development of metabolic dysfunction-associated steatohepatitis through oestrogen receptor alpha-dependent signalling. 2026;DOI:10.1038/s42255-025-01436-1.