Apolipoprotein B and triacylglycerol secretion in human triacylglycerol hydrolase transgenic mice

Autor: Enhui Wei, Mustafa Alam, Fengcheng Sun, Luis B. Agellon, Dennis E. Vance, Richard Lehner
Jazyk: angličtina
Rok vydání: 2007
Předmět:
Zdroj: Journal of Lipid Research, Vol 48, Iss 12, Pp 2597-2606 (2007)
Druh dokumentu: article
ISSN: 0022-2275
DOI: 10.1194/jlr.M700320-JLR200
Popis: Apolipoprotein B (apoB)-containing lipoproteins play a critical role in whole body lipid homeostasis and the pathogenesis of atherosclerosis. The assembly of hepatic apoB-containing lipoproteins, VLDL, is governed by the availability of lipids, including triacylglycerol (TG). The majority of TG associated with VLDL is derived from the hepatic cytoplasmic lipid stores by a process involving lipolysis followed by reesterification. Microsomal triacylglycerol hydrolase (TGH) has been demonstrated to play a role in the lipolysis/reesterification process. To evaluate the potential regulatory role of TGH in hepatic VLDL assembly, we developed inducible transgenic mice expressing a human TGH minigene under the control of the mouse metallothionein promoter. Induction of human TGH by zinc resulted in liver-specific expression of the enzyme associated with 3- to 4-fold increases in lipolytic activity that could be attenuated with a TGH-specific inhibitor. Augmented TGH activity led to increased secretion of newly synthesized apoB and plasma TG levels. These results suggest that increased hepatic expression of TGH leads to a more proatherogenic plasma lipid and apoB profile.
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