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Abstract

The nascent LD emanates from the outer membrane of the endoplasmic reticulum (ER; ►Fig. 1). This process is mainly driven by the coordinated activity of enzymes such as diacylglycerol O-acyltransferase 1 (DGAT1) and DGAT2 and acetyl-CoA acetyltransferase 1 (ACAT1) and ACAT2, which esterify fatty acids (FAs) and cholesterol, respectively. DGAT1 is only present in the ER membrane and uses diacylglycerol (DAG) derived from cytosolic triglyceride lipolysis to re-synthesize triglycerides in the ER lumen. DGAT2 localizes to both the ER and the LD membrane and synthesizes de novo triglycerides from FAs. 4,5 ACAT1 converts cholesterol into cholesteryl esters in the cytosol which are then incorporated into LDs to prevent cytotoxicity from cholesterol crystals. However, the product formed by ACAT2 is translocated to the ER and released in lipoproteins. 6,7 The resulting neutral lipids, namely triglycerides and cholesterol esters, form the core of hepatocellular LDs. The budding of nascent LDs from the ER outer Keywords ► steatotic liver disease ► lipid droplet ► lipid droplet proteins ► perilipins ► MASLD ► alcohol-associated liver disease ► hepatitis C