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ApoE and the role of very low density lipoproteins in adipose tissue inflammation.

ABSTRACT: To identify the role of triglyceride-rich lipoproteins (TGRLs) and apoE, a major apolipoprotein in TGRLs, in adipose tissue inflammation with high-fat diet (HFD)-induced obesity.Male apoE(-/-) and C57BL/6J wild-type (WT) mice fed HFD for 12 weeks were assessed for metabolic and inflammatory parameters. ApoE(-/-) and WT mice were orally gavaged with [(3)H]palmitic acid to examine the role of apoE in fat delivery to adipose tissue. VLDL from obese apoE(-/-) mice were intravenously injected into lean WT or apoE(-/-) mice to test potential contribution of TGRLs-derived fat delivery to inflammation in adipose tissue and the role of apoE.ApoE(-/-) mice gained less body weight, and had less fat mass and lower triglyceride levels in skeletal muscle than WT. ApoE(-/-) mice on HFD had better insulin sensitivity than WT even when comparing body weight-matched mice. Compared to WT mice, apoE(-/-) mice on HFD had lower levels of inflammatory cytokines/chemokines and CD11c in adipose tissue, and lower levels of inflammatory markers in skeletal muscle. At 6 h after oral gavage with [(3)H]palmitic acid, incorporation of [(3)H]palmitic acid into adipose tissue and skeletal muscle was lower in apoE(-/-) mice. After repeated daily injection for 3 days, VLDL from obese apoE(-/-) mice induced inflammation in adipose tissue of recipient WT but not apoE(-/-) mice.In HFD-induced obesity, apoE plays an important role in inflammation in adipose tissue and skeletal muscle, likely by mediating TGRL-derived fat delivery to these tissues.

SUBMITTER: Wang J

PROVIDER: S-EPMC3411924 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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ApoE and the role of very low density lipoproteins in adipose tissue inflammation.

Wang Jiali J Perrard Xiaoyuan Dai XD Perrard Jerry L JL Mukherjee Aparna A Rosales Corina C Chen Yuguo Y Smith C Wayne CW Pownall Henry J HJ Ballantyne Christie M CM Wu Huaizhu H

Atherosclerosis 20120619 2

<h4>Objective</h4>To identify the role of triglyceride-rich lipoproteins (TGRLs) and apoE, a major apolipoprotein in TGRLs, in adipose tissue inflammation with high-fat diet (HFD)-induced obesity.<h4>Methods</h4>Male apoE(-/-) and C57BL/6J wild-type (WT) mice fed HFD for 12 weeks were assessed for metabolic and inflammatory parameters. ApoE(-/-) and WT mice were orally gavaged with [(3)H]palmitic acid to examine the role of apoE in fat delivery to adipose tissue. VLDL from obese apoE(-/-) mice w ...[more]

PMID: 22770993

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Project description:It is uncertain whether pharmacological reductions in very-low-density lipoproteins (VLDLs), and their component triglyceride and cholesterol could reduce residual risk of atherosclerotic cardiovascular disease (ASCVD) events among individuals in whom low-density lipoprotein cholesterol (LDL-C) has been adequately lowered. We examined whether individuals with greater on-statin reductions in VLDL-related measures-beyond reductions in LDL-C-were at further reduced risk of ASCVD. In 9423 participants in the JUPITER (Justification for the Use of Statins in Prevention) trial (NCT00239681), at baseline and on statin we measured standard lipids, 400-MHz proton nuclear magnetic resonance spectroscopy-measured VLDL particle subclasses (small, medium, and large VLDL lipoprotein particle concentration), and total VLDL cholesterol mass. Compared with individuals allocated to placebo, we examined risk of incident ASCVD (N=211) among statin-allocated participants who achieved minimal (<median) or greater (≥median) marker reductions using adjusted Cox models. On-statin changes in VLDL-related markers were only modestly correlated (Spearman r≤0.29) with change in LDL-C. On-statin median LDL-C was 54 mg/dL and triglyceride was 101 mg/dL. Dose-response reductions in ASCVD risk were observed for greater reductions in LDL-C, VLDL cholesterol mass, and small VLDL lipoprotein particle concentration; the latter 2 remained significant after incremental adjustment for change in LDL-C (P≤0.006). Conversely, there was no further risk reduction with greater reductions in triglycerides or large/medium VLDL lipoprotein particle concentration. Pharmacological reduction in small, cholesterol-enriched, triglyceride-depleted VLDL was associated with reduction in ASCVD risk. Chemically measured triglycerides may not sufficiently capture risk related to VLDL pathways. These findings also support broader profiling of lipid and lipoprotein changes in response to statins as prognostic markers of individual benefit, supporting more precision-medicine, individualized approaches to cardiovascular risk reduction. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00239681.

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ApoE and the role of very low density lipoproteins in adipose tissue inflammation.

Publications

ApoE and the role of very low density lipoproteins in adipose tissue inflammation.

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