Low density lipoprotein delays clearance of triglyceride-rich lipoprotein by human subcutaneous adipose tissue

Simon Bissonnette,Huda Salem,Hanny Wassef,Nathalie Saint-Pierre,Annie Tardif,Alexis Baass,Robert Dufour,May Faraj

doi:10.1194/jlr.p023176

Simon Bissonnette, Huda Salem + Show 6 more

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https://doi.org/10.1194/jlr.p023176

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Abstract

Delayed clearance of triglyceride-rich lipoprotein (TRL) by white adipose tissue (WAT) promotes hypertriglyceridemia and elevated apoB-lipoproteins, which are primarily in the form of LDL. This study examines whether LDL promotes delayed clearance of TRL by WAT. Following the ingestion of a (13)C-triolein-labeled high-fat meal, obese women with high plasma apoB (> median 0.93 g/l, N = 11, > 98% as IDL/LDL) had delayed clearance of postprandial (13)C-triglyceride and (13)C-NEFA over 6 h compared with controls. AUC6 h of plasma (13)C-triglyceride and (13)C-NEFA correlated with plasma apoB but not with LDL diameter or adipocyte area. There was no group difference in (13)C-triolein oxidation rate, which suggests lower (13)C-NEFA storage in peripheral tissue in women with high apoB. Ex vivo/in vitro plasma apoB correlated negatively with WAT (3)H-lipid following a 4 h incubation of women's WAT with synthetic (3)H-triolein-TRL. LDL-differentiated 3T3-L1 adipocytes had lower (3)H-TRL hydrolysis and (3)H-NEFA storage. Treatment of women's WAT with their own LDL decreased (3)H-TRL hydrolysis and (3)H-NEFA uptake. Finally, LDL, although not an LPL substrate, reduced LPL-mediated (3)H-TRL hydrolysis as did VLDL and HDL. Exposure to LDL decreases TRL clearance by human WAT ex vivo. This may promote production of apoB-lipoproteins and hypertriglyceridemia through a positive-feedback mechanism in vivo.

Highlights

N (TRL) by white adipose tissue (WAT) promotes hypertriglyceridemia and elevated apoB-lipoproteins, which are primarily in the form of LDL
Data in this study demonstrate that plasma clearance of dietary TG and NEFA is delayed in postmenopausal obese women with high plasma apoB without any difference in the oxidation rate of NEFA, which points to reduced TG storage in peripheral tissue
Given the role of WAT in postprandial triglyceride-rich lipoprotein (TRL) clearance, we further examined the effects of apoB-lipoproteins on WAT function

Summary

Introduction

N (TRL) by white adipose tissue (WAT) promotes hypertriglyceridemia and elevated apoB-lipoproteins, which are primarily in the form of LDL. Following the ingestion of a 13C-triolein-labeled high-fat meal, obese women with high plasma apoB (> median 0.93 g/l, N = 11, > 98% as IDL/LDL) had delayed clearance of postprandial 13C-triglyceride and of plasma. Treatment of women’s WAT with their own LDL decreased 3H-TRL hydrolysis and 3H-NEFA uptake. Exposure to LDL decreases TRL clearance by human WAT ex vivo This may promote production of apoB-lipoproteins and hypertriglyceridemia through a positive-feedback mechanism in vivo.—Bissonnette, S., H. Efficient clearance of chylomicrons by WAT requires three sequential steps: i) the hydrolysis of chylomicrons by endothelial lipoprotein lipase (LPL); ii) the uptake of LPL-generated nonesterified fatty acid (NEFA) by underlying adipocytes; and iii) the utilization or storage of NEFA [3, 5]. Dietary TRL remnants and NEFA that are not cleared by peripheral tissue are taken up by the liver for utilization and resecretion as VLDL (TRL with apoB100)

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