White Adipose Tissue Apolipoprotein C-I Secretion in Relation to Delayed Plasma Clearance of Dietary Fat in Humans

Author:

Wassef Hanny1,Salem Huda1,Bissonnette Simon1,Baass Alexis1,Dufour Robert1,Davignon Jean1,Faraj May1

Affiliation:

1. From the Institut de recheches cliniques de Montréal (IRCM), Montréal, Québec, Canada (H.W., H.S., S.B., A.B., R.D., J.D., M.F.); Department of Medicine, Division of Experimental Medicine, McGill University, Montréal, Québec, Canada (H.W., A.B., J.D.); Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada (H.S., S.B., R.D., J.D., M.F.); and Montreal Diabetes Research Center (MDRC), Montréal, Québec, Canada (M.F.).

Abstract

Objective— White adipose tissue (WAT) dysfunction is characterized by delayed clearance of dietary triglyceride-rich lipoproteins (TRL). We reported that apolipoprotein (apo) C-I, a transferable apolipoprotein that inhibits lipoprotein lipase activity when bound to TRL, was produced by a human adipocyte model. Thus, we aimed to determine whether increased WAT apoC-I secretion is related to delayed dietary fat clearance in humans. Methods and Results— After the ingestion of a 13 C-triolein–labeled high-fat meal, postmenopausal obese women with high-fasting WAT apoC-I secretion (median >0.81 μmol/L per g/4 hours, n=9) had delayed postprandial plasma clearance of 13 C-triglyceride and 13 C-nonesterified fatty acids over 6 hours compared with controls. WAT apoC-I secretion over 4 hours correlated with fasting total and non–high-density lipoprotein apoC-I but not with high-density lipoprotein apoC-I and was the primary predictor of 4-hour postprandial increases in TRL apoC-I. Correction for TRL apoC-I eliminated the association of WAT apoC-I with 6-hour area under the curve of plasma 13 C-triglyceride; correction for insulin sensitivity or inflammation did not. Finally, in addition to apoC-I, WAT secreted considerable amount of apoC-II, apoC-III, and apoE over 24 hours; however, only WAT apoC-I secretion was associated with 6-hour area under the curve of plasma 13 C-triglyceride. Conclusion— Increased WAT apoC-I secretion in obese women is associated with delayed postprandial dietary fat clearance mediated by increased TRL apoC-I. Thus, we hypothesize that reducing WAT apoC-I secretion ameliorates WAT dysfunction and associated cardiometabolic risks in humans.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

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