4.7 Article

Enhanced cholesterol efflux to HDL through the ABCA1 transporter in hypertriglyceridemia of type 2 diabetes

Journal

METABOLISM-CLINICAL AND EXPERIMENTAL
Volume 63, Issue 5, Pages 727-734

Publisher

W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.metabol.2014.03.001

Keywords

HDL; Efflux; ABCA-1; Triglycerides; CETP; Diabetes

Funding

  1. USC CTSI pilot [UL1TR000130]
  2. NIEHS [P30ES06694]
  3. [K23HL107389]
  4. [AHAl2CRP11750017]

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Objective. Our objective was to examine the role of hypertriglyceridemia on the capacity of HDL to facilitate ABCA-1 mediated cholesterol efflux in type 2 diabetes (T2DM). Methods. HDL mediated cholesterol efflux through the ABCA-1 transporter was measured using BHK cell lines in samples of 71 participants with T2DM in the presence or absence of high triglyceride levels (TG). Additionally, HDL mediated efflux was measured in 13 diabetic and non-diabetic participants fasting and four hours after a high-fat test challenge. Results. HDL mediated cholesterol efflux function was increased in participants with T2DM with hypertriglyceridemia when compared to participants with T2DM without hypertriglyceridemia (efflux ratio mean +/- standard deviation (SD), T2DM + TG: 1.17 +/- 0.25 vs. T2DM - TG: 1.03 +/- 0.19, p = 0.0098). In the fat challenge study, we observed a significant increase in ABCA-1 mediated cholesterol efflux capacity following an ingestion of high-fat test meal by participants in both groups of T2DM (n = 6, efflux ratio, mean +/- SD, pre: 0.86 +/- 0.4 vs. post: 1.34 +/- 0.6, p = 0.01) and non-diabetic participants (n = 7, efflux ratio mean +/- SD pre: 1.24 +/- 0.31 vs. post: 1.39 +/- 0.42, p = 0.04) that was partly explained by the difference in CETP activity (r = 0.6, p = 0.03). Conclusion. Our study suggests that high triglyceride levels facilitate ABCA-1 mediated efflux function of HDL in part by activating CETP. (C) 2014 Elsevier Inc. All rights reserved.

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