Synthesis and Secretion of ApoC-I and ApoE during Maturation of Human SW872 Liposarcoma Cells

Salem

et al. 2012

ATVB

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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 highfasting 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

Section: Discussionmentioning

confidence: 72%

mentioning

confidence: 99%

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

Salem

et al. 2012

ATVB

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“…We were the first to report the secretion of apoC-I from a human adipocyte model (27) and by human subcutaneous WAT ex vivo (14). Moreover, we demonstrated that WAT secretion of apoC-I, but not of apoC-II, apoC-III, or apoE, was correlated with delayed postprandial plasma clearance of dietary TRL in postmenopausal overweight and obese women (14), while no data existed for men.…”

Section: Apoc-i Secretion From Subjects' Wat Samples Ex Vivo (N = 39)mentioning

confidence: 86%

WAT apoC-I secretion: role in delayed chylomicron clearance in vivo and ex vivo in WAT in obese subjects

Cyr

Journal of Lipid Research

et al. 2016

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The cardiometabolic risk associated with reduced HDL cholesterol (HDL-C) and/or elevated LDL cholesterol (LDL-C) has been well-established, the cardiometabolic risk associated with elevated TG-rich lipoproteins (TRLs) has not. However, elevated concentrations of TRLs have received much interest lately given their association with obesity, insulin resistance, and type 2 diabetes (1, 2). Two recent meta-analyses identified hypertriglyceridemia as a predictor of cardiovascular disease (3, 4). Although controversy exists regarding the independent contribution of fasting hypertriglyceridemia because of its inverse relationship with HDL-C (3, 5), that of postprandial hypertriglyceridemia remains sturdy even after adjustment for HDL-C (5-7). Accordingly, much research has now focused on factors that regulate postprandial TRL clearance.Clearance of postprandial TRLs is highly dependent on white adipose tissue (WAT). A fundamental function of WAT in the postprandial state is the hydrolysis of the TG core of TRLs through the activity of endothelial LPL and the uptake and storage of released NEFAs (8-10). Dysfunctional WAT has reduced metabolic flexibility and is unable to switch promptly from fasting (catabolic) to postprandial (anabolic) state. This leads to delayed TRL clearance, impaired remodeling of circulating lipoproteins, and increased TRL flux to peripheral tissues; thereby increasing cardiometabolic risks (11,12). The underlying mechanisms promoting WAT dysfunction and delayed TRL clearance are not fully understood.

“…The cholesterol concentrations measured by these two techniques were highly correlated (TRL, r = 0.82; IDL/LDL, r = 0.92; P < 0.0001), indicating the reliability of the FPLC fractionation of the lipoproteins. ApoB and apoE concentrations in 80 FPLC fractions were quantifi ed by in-house ELISA using polyclonal antibodies against human apolipoproteins (Academy Biomedical) as published ( 36,43 ). LDL was isolated from fresh fasting plasma by sequential ultracentrifugation using KBr density solution (1.019-1.063 g/ml, 0.01% EDTA) and Beckman Ti-50 rotor (45,000 rpm, 32 h, 5°C), after removal of TRL and IDL (density < 1.019 g/ml).…”

Section: Lipoprotein Profi Ling and Ldl Isolationmentioning

confidence: 99%

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

Salem

Journal of Lipid Research

et al. 2013

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This article is available online at http://www.jlr.org among the most common is reduced triglyceride-rich lipoprotein (TRL) clearance by peripheral tissue. White adipose tissue (WAT) is a major regulator of TRL clearance, particularly in the postprandial state ( 2-6 ). Following a meal, dietary fat enters the circulation in the form of chylomicrons, TRL with apoB48. Effi cient 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 nonesterifi ed 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 then taken up by the liver for utilization and resecretion as VLDL (TRL with apoB100).Healthy WAT is able to respond promptly to postprandial signals, such as insulin increasing the hydrolysis of dietary TRL and the uptake and storage of generated NEFA, thus reestablishing the homeostasis in plasma lipids. The storage versus the release of TRL-generated NEFA in human subcutaneous WAT was reported to be almost absent in the fasting state, to increase to 100% 1 h after the ingestion of a meal, and to decrease to 10-30% 6 h after the meal ( 5 ). Accordingly, delayed plasma clearance of postprandial TRL by WAT is believed to increase the infl ux of dietary TRL remnants and NEFA into nonadipose peripheral tissues, including muscle, pancreas, and liver, inducing lipotoxicity and insulin resistance ( 6-8 ). In the liver, this also leads to increased synthesis and secretion of VLDL, which further reduces chylomicron clearance due to competitive binding to LPL ( 9-14 ). Altogether, this increases the plasma concentrations of apoB-lipoproteins, which is measured as plasma apoB and represents mostly LDL particles (>90%) ( 14-16 ). Dysfunctional WAT is thus Postprandial hypertriglyceridemia is an independent risk factor for cardiometabolic disease ( 1 ). Many factors have been implicated in the etiology of hyperlipidemia;