@article{e032d45ad2eb49b3af41dfa310bf5a5f,
title = "CETP inhibition improves hdl function but leads to fatty liver and insulin resistance in CETP-expressing transgenic mice on a high-fat diet",
abstract = "In clinical trials, inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels but does not robustly improve cardiovascular outcomes. Approximately two-thirds of trial participants are obese. Lower plasma CETP activity is associated with increased cardiovascular risk in human studies, and protective aspects of CETP have been observed in mice fed a high-fat diet (HFD) with regard to metabolic outcomes. To define whether CETP inhibition has different effects depending on the presence of obesity, we performed short-term anacetrapib treatment in chow- and HFD-fed CETP transgenic mice. Anacetrapib raised HDL cholesterol and improved aspects of HDL functionality, including reverse cholesterol transport, and HDL's antioxidative capacity in HFD-fed mice was better than in chow-fed mice. Anacetrapib worsened the anti-inflammatory capacity of HDL in HFD-fed mice. The HDL proteome was markedly different with anacetrapib treatment in HFD- versus chow-fed mice. Despite benefits on HDL, anacetrapib led to liver triglyceride accumulation and insulin resistance in HFD-fed mice. Overall, our results support a physiologic importance of CETP in protecting from fatty liver and demonstrate context selectivity of CETP inhibition that might be important in obese subjects.",
author = "Lin Zhu and Thao Luu and Emfinger, {Christopher H.} and Parks, {Bryan A.} and Jeanne Shi and Elijah Trefts and Fenghua Zeng and Zsuzsanna Kuklenyik and Harris, {Raymond C.} and Wasserman, {David H.} and Sergio Fazio and Stafford, {John M.}",
note = "Funding Information: Funding. This study was supported by the Vanderbilt Hormone Assay Core (NIH grant DK-020593), Vanderbilt Mouse Metabolic Phenotyping Core (NIH grant DK-59637), Vanderbilt Diabetes Research and Training Center (P30-DK-020593 and P30-DK-058404), and Vanderbilt O{\textquoteright}Brien Kidney Center (DK-114809). S.F. was supported by NIH grant R01-HL-132985, and J.M.S. was supported by the Department of Veterans Affairs (BX002223) and NIH grant R01-DK-109102. Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. L.Z. wrote the manuscript and researched data. T.L., C.H.E., B.A.P., J.S., E.T., F.Z., and Z.K. researched data and reviewed the manuscript. R.C.H. and D.H.W. reviewed and edited the manuscript. S.F. contributed to the discussion and reviewed and edited the manuscript. J.M.S. researched data, contributed to the discussion, and reviewed and edited the manuscript. J.M.S. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Publisher Copyright: {\textcopyright} 2018 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license..",
year = "2018",
month = dec,
day = "1",
doi = "10.2337/db18-0474",
language = "English (US)",
volume = "67",
pages = "2494--2506",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "12",
}