Reduced Reverse Cholesterol Transport Efficacy in Healthy Men with Undesirable Postprandial Triglyceride Response.

Abstract

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.

• Authors: Alexandre Motte Motte, Julie Gall Gall, Joe-Elie Salem, Eric Dasque, Martine Lebot, Eric Frisdal, Sophie Galier, Elise F Villard, Elodie Bouaziz-Amar, Jean-Marc Lacorte, Beny Charbit, Wilfried Le Goff, Philippe Lesnik, Maryse Guerin
• Journal: Biomolecules (Biomolecules) Vol. 10 Issue 5 (05 25 2020) ISSN: 2218-273X [Electronic] Switzerland
• PMID: 32466286 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CETP protein, human
• Cholesterol Ester Transfer Proteins
• Cholesterol Esters
• Chylomicrons
• HDL cholesteryl ester
• Lipoproteins, HDL
• Triglycerides
• Cholesterol

Topics

• Adult
• Cholesterol (metabolism)
• Cholesterol Ester Transfer Proteins (metabolism)
• Cholesterol Esters (metabolism)
• Chylomicrons (metabolism)
• Humans
• Hypertriglyceridemia (metabolism)
• Lipoproteins, HDL (metabolism)
• Liver (metabolism)
• Macrophages (metabolism)
• Male
• Postprandial Period
• Triglycerides (blood, metabolism)