Inhibitors of hepatic microsomal triacylglycerol hydrolase decrease very low density lipoprotein secretion

SPECIFIC AIMSTriacylglycerol hydrolase (TGH) is an intracellular lipase that has been proposed to catalyze the mobilization of hepatic triacylglycerol (TG) stores for very low density lipoprotein (VLDL) assembly. The aim of the current study was to examine the effects of inhibition of this lipase activity on lipid and apolipoprotein (apo) B synthesis and secretion, revealing a potential pharmacological target for reducing risk of coronary artery disease and stoke from atherosclerosis.PRINCIPAL FINDINGS1. Diethyl-p-nitrophenylphosphate (E600) inhibits TGH activityWe have previously reported the purification of a hepatic TGH and hypothesized that this lipase is involved in mobilizing stored TG for VLDL assembly via a lipolysis and reesterification pathway. The present research explores the relationship between TGH and the provision of lipid for VLDL and apoB secretion. TGH has been localized to the endoplasmic reticulum (ER) and can associate with lipid droplets. The enzyme is absent from the liver-derived ...