@article{fdd8d9363db14afea804f800c927d39f,
title = "Endothelial cell CD36 optimizes tissue fatty acid uptake",
abstract = "Movement of circulating fatty acids (FAs) to parenchymal cells requires their transfer across the endothelial cell (EC) barrier. The multiligand receptor cluster of differentiation 36 (CD36) facilitates tissue FA uptake and is expressed in ECs and parenchymal cells such as myocytes and adipocytes. Whether tissue uptake of FAs is dependent on EC or parenchymal cell CD36, or both, is unknown. Using a cell-specific deletion approach, we show that EC, but not parenchymal cell, CD36 deletion increased fasting plasma FAs and postprandial triglycerides. EC-Cd36-KO mice had reduced uptake of radiolabeled long-chain FAs into heart, skeletal muscle, and brown adipose tissue; these uptake studies were replicated using [11C]palmitate PET scans. High-fat diet-fed EC-CD36-deficient mice had improved glucose tolerance and insulin sensitivity. Both EC and cardiomyocyte (CM) deletion of CD36 reduced heart lipid droplet accumulation after fasting, but CM deletion did not affect heart glucose or FA uptake. Expression in the heart of several genes modulating glucose metabolism and insulin action increased with EC-CD36 deletion but decreased with CM deletion. In conclusion, EC CD36 acts as a gatekeeper for parenchymal cell FA uptake, with important downstream effects on glucose utilization and insulin action.",
author = "Son, {Ni Huiping} and Debapriya Basu and Dmitri Samovski and Pietka, {Terri A.} and Peche, {Vivek S.} and Florian Willecke and Xiang Fang and Yu, {Shui Qing} and Diego Scerbo and Chang, {Hye Rim} and Fei Sun and Svetlana Bagdasarov and Konstantinos Drosatos and Yeh, {Steve T.} and Mullick, {Adam E.} and Shoghi, {Kooresh I.} and Namrata Gumaste and Kim, {Kyeong Jin} and Huggins, {Lesley Ann} and Tenzin Lhakhang and Abumrad, {Nada A.} and Goldberg, {Ira J.}",
note = "Funding Information: We thank Stephanie Chiang and Sunny Son for help with manuscript preparation and data analysis, Yun-ying Hu (New York University School of Medicine) for the kinetic studies, and Chyu-an-Sheng Lin at the Columbia University Transgenic mouse Core for the generation of floxed mice by pronuclear DNA microinjection and embryo transfer. We thank the New York University Langone Medical Center OCS Microscopy Core, specifically Alice Liang, Kristen Dancel, and Yan Deng, for their consultation and assistance with transmission electron microscopic work. We also thank Nikki Fettig at the Radiological Chemistry and Imaging Laboratory (RCIL) of the Mallinckrodt Institute of Radiology at Washington University for assistance with the [11C]palmitate and [18F]DG studies. We also thank A. Tall (Columbia University Medical Center), C. Semenkovich (Washington University School of Medicine), R. Kitsis (Department of Medicine, Albert Einstein College of Medicine, New York, New York, USA), and W. Blaner (Columbia University Medical Center) for constructive comments made during the preparation of this manuscript. The studies were funded by National Heart, Blood, and Lung Institute grants HL45095 and HL73029 (to IJG) and DK33301 and DK11175 (to NAA). Publisher Copyright: {\textcopyright} 2018 American Society for Clinical Investigation. All rights reserved.",
year = "2018",
month = oct,
day = "1",
doi = "10.1172/JCI99315",
language = "English",
volume = "128",
pages = "4329--4342",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
number = "10",
}