Coagulation protease-activated receptor-2 (PAR2) promotes dyslipidemia, obesity and MASLD through repression of the hepatic pioneer factor HNF4α
Blocking a coagulation receptor protects against fatty liver disease in mice, with a drug candidate showing promise for obesity-related cardiometabolic disease.
This study links the coagulation factor Xa receptor PAR2 to MASLD/MASH progression through a PAR2–cJun–HNF4α pathway that impairs hepatic lipid metabolism; PAR2 is 5-7x elevated in obese human liver specimens and hepatocyte-specific deletion confers protection in diet-induced obese mice. A liver-homing PAR2 pepducin inhibitor (OA-235i) reduces weight gain and improves liver histology, establishing a novel cardiometabolic drug target with human translational evidence.
What the study was
- Study design
- Cross-sectional human study + mechanistic mouse model
- Population
- Obese vs non-obese patients with MASLD/MASH (n=105 liver specimens) + hepatocyte-specific PAR2 knockout mice
- Sample size
- 105
- Category
- Drug Development
- Maturity
- Exploratory
- Journal
- JHEP Reports
Why it surfaced
Novel PAR2 target with human translational evidence (n=105) and drug-like inhibitor data; triage_score capped at 5 for mixed human/animal study without clinical trial data; COI noted (founders of Oasis Pharmaceuticals)
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