Author information

¹Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, USA.

²Department of Integrated Biology and Physiology, University of Minnesota, Minneapolis, MN, USA.

³Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, University of Minnesota, Minneapolis, MN, USA.

⁴Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, USA.

Abstract

Hepatic steatosis, the buildup of neutral lipids in lipid droplets (LDs), is commonly referred to as metabolic dysfunction-associated steatotic liver disease (MASLD) when alcohol or viral infections are not involved. MASLD encompasses simple steatosis and the more severe metabolic dysfunction-associated steatohepatitis (MASH), characterized by inflammation, hepatocyte injury, and fibrosis. Previously viewed as inert markers of disease, LDs are now understood to play active roles in disease etiology and have significant non-pathological and pathological functions in cell signaling and function. These dynamic properties of LDs are tightly regulated by hundreds of proteins that coat the LD surface, controlling lipid metabolism, trafficking, and signaling. The following review highlights various facets of LD biology with the primary goal of discussing key mechanisms through which LDs can promote the development of advanced liver diseases including MASH.