2007 Robert Levy Memorial Lecture—Triglyceride: Nutrient and Toxin
How does an essential nutrient, required for energy and cellular structure, become a major toxin? When we over-nourish ourselves, excess carbohydrate calories (after conversion to triglycerides) circulate in very-low-density lipoprotein, and dietary triglycerides circulate in chylomicrons. Both of these particles interact with lipoprotein lipase (LpL), a dimeric enzyme located on the luminal surface of endothelial cells and on cardiomyocytes. LpL releases fatty acids from triglyceride and allows them to be taken up by cells. Thus, LpL is central to the creation of LDL and the regulation of HDL.
Lipolysis of triglyceride is beneficial, but when it occurs in excess and along the arterial wall, it can be detrimental. Both tissue culture and limited animal experimental data suggest that excess products of LpL lipolysis activate inflammatory molecules and alter vascular function.
The organ of the body that most actively metabolizes triglyceride is the heart. This ultimate marathon muscle uses primarily fatty acids as its energy source. Like most tissues, though, the heart can switch and run on glucose. In ischemia, this process is beneficial, but only to an extent: Total loss of LpL-derived lipids is harmful in experimental animals. However, excess accumulation of lipids is also detrimental and leads to the lipotoxic dilated cardiomyopathy that occurs with diabetes and obesity. Because triglyceride can be good or bad, cells and organs need to control their appetites.