Blocking Key Fat Metabolic Enzyme Lowers Blood Triglyceride Levels

Inhibition of a key enzyme of fat metabolism lowers serum triglyceride levels and reduces amounts of cardiovascular disease risk indicators such as apolipoprotein B while increasing insulin sensitivity and glucose tolerance.

Excessive accumulation of triglycerides in peripheral tissues is closely associated with obesity and has been identified as an independent risk factor for insulin resistance, type II diabetes, and cardiovascular complications. Triglycerides are released into the blood stream through the action of the enzyme triacylglycerol hydrolase (TGH, also known as carboxylesterase-3, Ces3). In the current study, investigators from the University of Alberta (Edmonton, Canada) sought to improve the blood lipid profile by inhibiting the activity of TGH.

The investigators genetically engineered a line of mice to lack the gene for TGH. They reported in the March 3, 2010, edition of the journal Cell Metabolism that these TGH-null animals showed decreased plasma triglycerides, apolipoprotein B, and fatty acid levels in both fasted and fed states. These mice exhibited increased food intake and energy expenditure without change in body weight, and these metabolic changes were accompanied by improved insulin sensitivity and glucose tolerance. Despite a reduction in the level of very low-density lipoprotein (VLDL) secretion, TGH deficiency did not increase the amount of triglycerides in the animals' livers.

The authors concluded that, "These studies demonstrate the potential of TGH as a therapeutic target for lowering blood lipid levels.”

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