Apolipoprotein B and triacylglycerol secretion in human triacylglycerol hydrolase transgenic mice.
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.
Wei
Enhui
E
Department of Pediatrics, Canadian Institutes of Health Research Group on the Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
Alam
Mustafa
M
Sun
Fengcheng
F
Agellon
Luis B
LB
Vance
Dennis E
DE
Lehner
Richard
R
D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D008049:Lipase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D013997:Time Factors; D014162:Transfection; D014280:Triglycerides / Q000378:metabolism*
D001055:Apolipoproteins B; D014280:Triglycerides; D008668:Metallothionein; D008049:Lipase