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

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 C-13-triolein-labeled high-fat meal, postmenopausal obese women with high-fasting WAT apoC-I secretion (median >0.81 mu mol/L per g/4 hours, n=9) had delayed postprandial plasma clearance of C-13-triglyceride and C-13-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 C-13-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 C-13-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. (Arterioscler Thromb Vasc Biol. 2012;32:2785-2793.)