Subcellullar localization, developmental expression and characterization of a liver triacylglycerol hydrolase

The mechanism and enzymic activities responsible for the lipolysis of store d cytosolic triacylglycerol in liver and its reesterification remain obscur e. A candidate enzyme for lipolysis, a microsomal triacylglycerol hydrolase (TGH), was recently purified to homogeneity from pig liver and its kinetic properties were determined [Lehner and Verger (1997) Biochemistry 36, 1861 -1868]. We have characterized the enzyme with regard to its species distrib ution, subcellular localization, developmental expression and reaction with lipase inhibitors. The hydrolase cosediments with endoplasmic reticulum el ements and is associated with isolated liver fat droplets. Immunocytochemic al studies localize TGH exclusively to liver cells surrounding capillaries. Both TGH mRNA and protein are expressed in rats during weaning. The enzyme covalently binds tetrahydrolipstatin, an inhibitor of lipases and of triac ylglycerol hydrolysis. The enzyme is absent from liver-derived cell lines ( HepG2 and McArdle RH7777) known to be impaired in very-low-density lipoprot ein (VLDL) assembly and secretion. The localization and developmental expre ssion of TGH are consistent with a proposed role in triacylglycerol hydroly sis and with the proposal that some of the resynthesized triacylglycerol is utilized for VLDL secretion.