HSD17β11 regulates PLIN5-ATGL mediated lipolysis, but not hepatic lipid metabolism in mice

Abstract

Hydroxysteroid 17β dehydrogenase 11 (HSD17β11) is a member of the 17β-HSD family with canonical roles in steroid metabolism. Given its predominant localization on lipid droplets, we investigated HSD17β11's role in lipid metabolism. In patients with metabolic dysfunction-associated fatty liver disease (MASLD), liver HSD17β11 levels are reduced, correlating with liver steatosis severity. HSD17β11 deletion in human cell lines increased lipid droplet size and number. This is associated with triglyceride accumulation due to impaired lipolysis and increased fatty acid uptake. Mechanistically, HSD17β11 facilitates the interaction between PLIN5 and ATGL, enabling efficient protein kinase A (PKA)-sti..