Mechanism of HDL Lowering In Insulin Resistant States

Abstract

Hypertriglyceridemia and low plasma HDL-cholesterol (HDL-c) are the lipid abnormalities that typically occur as a consequence of insulin resistant conditions, including abdominal obesity, impaired fasting glucose and Type 2 diabetes. HDL-c and apolipoprotein A-1 (apo A-1, the major protein moiety of HDL particles) are inversely associated with plasma triglycerides (TG). In fact, the majority of individuals who have HDL-c levels below the 10^th percentile for age and gender have some degree of fasting and/or postprandial hypertriglyceridemia, insulin resistance and abdominal obesity. Hypertriglyceridemia is due predominantly to elevated very low density lipoprotein (VLDL) production by the liver in the fasting state and delayed clearance of intestinally-derived chylomicrons and hepatically-derived VLDL in the postprandial state. In hypertriglyceridemic states there is active lipid exchange between TG-rich lipoproteins (VLDL and chylomicrons) and HDL. We hypothesise that TG enrichment of HDL particles, followed by lipolytic modification by HL, enhances the clearance of HDL particles from the circulation, ultimately lowering plasma HDL-c concentrations. Since we have recently reviewed in detail the various lines of evidence in support of this hypothesis,¹ the present brief review will summarize only our own recent work in this area.