Team identifies HIF2A as liver disease target

A paper published in Nature Medicine by researchers at the National Cancer Institute and colleagues identified intestinal endothelial PAS domain protein 1 (HIF2A; HIF-2alpha; EPAS1) as a promising target to treat hepatic steatosis. The findings suggest a new indication for small molecule HIF2A inhibitors including PT2385 from Peloton Therapeutics Inc. (Dallas, Texas), which was used in the study.

Researchers identified that HIF2A had increased expression in distal ileum patient biopsies from obese individuals compared with non-obese individuals. When the researchers examined high-fat diet (HFD)-fed mice, they observed that genetic deletion of intestinal HIF2A resulted in decreased body weight gain, improved insulin sensitivity and decreased lipid droplet accumulation in the liver compared with genetically healthy mice. Levels of hepatic cholesterol and triglycerides were also decreased in intestine-specific HIF2A knockout mice on HFD compared with genetically normal HFD mice...