α/β-Hydrolase Domain-Containing 6 (ABHD6)- A Multifunctional Lipid Hydrolase.

α/β-hydrolase domain-containing 6 (ABHD6) belongs to the α/β-hydrolase fold superfamily and was originally discovered in a functional proteomic approach designed to discover monoacylglycerol (MAG) hydrolases in the mouse brain degrading the endocannabinoid 2-arachidonoylglycerol. Subsequent studies confirmed that ABHD6 acts as an MAG hydrolase regulating cannabinoid receptor-dependent and -independent signaling processes. The enzyme was identified as a negative modulator of insulin secretion and regulator of energy metabolism affecting the pathogenesis of obesity and metabolic syndrome.

KIAA1363 affects retinyl ester turnover in cultured murine and human hepatic stellate cells.

Large quantities of vitamin A are stored as retinyl esters (REs) in specialized liver cells, the hepatic stellate cells (HSCs). To date, the enzymes controlling RE degradation in HSCs are poorly understood. In this study, we identified KIAA1363 (also annotated as arylacetamide deacetylase 1 or neutral cholesterol ester hydrolase 1) as a novel RE hydrolase.

Lysosomal acid lipase is the major acid retinyl ester hydrolase in cultured human hepatic stellate cells but not essential for retinyl ester degradation.

Vitamin A is stored as retinyl esters (REs) in lipid droplets of hepatic stellate cells (HSCs). To date, two different pathways are known to facilitate the breakdown of REs: (i) Hydrolysis of REs by neutral lipases, and (ii) whole lipid droplet degradation in autolysosomes by acid hydrolysis. In this study, we evaluated the contribution of neutral and acid RE hydrolases to the breakdown of REs in human HSCs.

Hepatocyte-specific deletion of lysosomal acid lipase leads to cholesteryl ester but not triglyceride or retinyl ester accumulation.

Lysosomal acid lipase (LAL) hydrolyzes cholesteryl ester (CE) and retinyl ester (RE) and triglyceride (TG). Mice globally lacking LAL accumulate CE most prominently in the liver. The severity of the CE accumulation phenotype progresses with age and is accompanied by hepatomegaly and hepatic cholesterol crystal deposition.