Acyl coenzyme A: cholesterol acyltransferase inhibition and hepatic apolipoprotein B secretion

Acyl coenzyme A: cholesterol acyltransferase (ACAT) is postulated to play a role in hepatic and intestinal lipoprotein secretion. There is accumulatin g evidence, both in vitro and in vivo, that cholesterol and/or cholesteryl ester availability can regulate hepatic VLDL secretion. How ACAT inhibition regulates the assembly and secretion of apolipoprotein (apo) B containing lipoproteins within the hepatocyte has not been clearly established. ApoB k inetic studies performed in animals indicate that reduction in VLDL apoB se cretion is an important mechanism whereby ACAT inhibitors decrease the plas ma concentrations of these lipoproteins. However, in cultured hepatocytes, the effect of ACAT inhibition on apoB secretion has been inconsistent. Rece nt evidence has suggested the existence of more than one ACAT enzyme in mam mals, which has culminated in the recent cloning of ACAT2. ACAT1 and ACAT2 respond differently to ACAT inhibitors of differing structures and classes. ACAT2 is present in the liver and intestine, the sites of apoB containing lipoprotein secretion and may represent the enzyme responsible for generati ng cholesteryl esters destined for lipoprotein assembly and secretion. (C) 1999 Elsevier Science B.V. All rights reserved.