Cholesterol Intake Modulates Plasma Triglyceride Levels in Glycosylphosphatidylinositol HDL-Binding Protein 1-Deficient Mice

Abstract

Objective— To determine whether plasma triglyceride levels in adult Glycosylphosphatidylinositol HDL-binding protein 1 (GPIHBP1)-deficient ( Gpihbp1 −/− ) mice would be sensitive to cholesterol intake. Methods and Results— Gpihbp1 −/− mice were fed a Western diet containing 0.15% cholesterol. After 4 to 8 weeks, their plasma triglyceride levels were 113 to 135 mmol/L. When 0.005% ezetimibe was added to the diet to block cholesterol absorption, Lpl expression in the liver was reduced significantly, and the plasma triglyceride levels were significantly higher (>170 mmol/L). We also assessed plasma triglyceride levels in Gpihbp1 −/− mice fed Western diets containing either high (1.3%) or low (0.05%) amounts of cholesterol. The high-cholesterol diet significantly increased Lpl expression in the liver and lowered plasma triglyceride levels. Conclusion— Treatment of Gpihbp1 −/− mice with ezetimibe lowers Lpl expression in the liver and increases plasma triglyceride levels. A high-cholesterol diet had the opposite effects. Thus, cholesterol intake modulates plasma triglyceride levels in Gpihbp1 −/− mice.