Liver Enzyme Modulates Production of Pro-Atherosclerosis Lipoproteins

A recent publication described how production of the pro-atherosclerosis apoB component of the very low-density lipoproteins (VLDLs) is modulated by the activity of the liver enzyme triacylglycerol hydrolase (TGH).

Investigators from the University of Alberta (Edmonton, Canada) genetically engineered a line of mice that expressed a human TGH minigene under the control of the mouse metallothionein promoter. They reported in the December 2007 issue of the Journal of Lipid Research that induction of the human TGH gene by zinc resulted in liver-specific expression of the enzyme associated with three- to four-fold increases in lipolytic activity. This activity could be reduced with a TGH-specific inhibitor. Increased TGH activity led to increased secretion of newly synthesized apoB and higher plasma triglyceride levels.

"There is a substantial pharmacological interest in the enzymes that control triglyceride and cholesterol metabolism in tissues,” said senior author Dr. Richard Lehner, professor of cell biology at the University of Alberta. "We established the proof of principle of how these metabolic pathways work. We discovered the activity of an enzyme that releases fatty acids from fat cells and the liver into the blood and how to inhibit this from happening.”

The investigators warned that even if a drug were to be developed to control TGH activity, it would have to be combined with significant life-style changes (loss of weight, exercise, proper diet, etc.) to be effective.


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