An undesirable postprandial triglyceride response enhances CETP-mediated cholesteryl ester transfer to chylomicrons and reduces hepatic HDL cholesteryl ester uptake (Biomolecules 2020)

Elevation of nonfasting triglyceride (TG) levels above 1.8 g/L (2 mmol/L) is associated with increased risk of cardiovascular diseases. Exacerbated postprandial hypertriglyceridemia (PP-HTG) and metabolic context both modulate the overall efficacy of the reverse cholesterol transport (RCT) pathway, but the specific contribution of exaggerated PP-HTG on RCT efficacy remains indeterminate. Healthy male volunteers (n = 78) exhibiting no clinical features of metabolic disorders underwent a postprandial exploration following consumption of a typical Western meal providing 1200 kcal. Subjects were stratified according to maximal nonfasting TG levels reached after ingestion of the test meal into subjects with a desirable PP-TG response (GLow, TG < 1.8 g/L, n = 47) and subjects with an undesirable PP-TG response (GHigh, TG > 1.8 g/L, n = 31). The impact of the degree of PP-TG response on major steps of RCT pathway, including cholesterol efflux from human macrophages, cholesteryl ester transfer protein (CETP) activity, and hepatic high-density lipoprotein (HDL)-cholesteryl ester (CE) selective uptake, was evaluated. Cholesterol efflux from human macrophages was not significantly affected by the degree of the PP-TG response. Postprandial increase in CETP-mediated CE transfer from HDL to triglyceride-rich lipoprotein particles, and more specifically to chylomicrons, was enhanced in GHigh vs GLow. The hepatic HDL-CE delivery was reduced in subjects from GHigh in comparison with those from GLow. Undesirable PP-TG response induces an overall reduction in RCT efficacy that contributes to the onset elevation of both fasting and nonfasting TG levels and to the development of cardiometabolic diseases.