1. Endothelial cell CD36 optimizes tissue fatty acid uptake
- Author
-
Shuiqing Yu, Steve T Yeh, Xiang Fang, Nada A. Abumrad, Ni-Huiping Son, Dmitri Samovski, Tenzin Lhakhang, Konstantinos Drosatos, Ira J. Goldberg, Kooresh I. Shoghi, Namrata Gumaste, Svetlana Bagdasarov, Florian Willecke, Fei Sun, Lesley-Ann Huggins, Adam E. Mullick, Vivek S. Peche, Terri A. Pietka, Diego Scerbo, Kyeong Jin Kim, Debapriya Basu, and Hye Rim Chang
- Subjects
0301 basic medicine ,CD36 Antigens ,medicine.medical_specialty ,medicine.medical_treatment ,CD36 ,Biological Transport, Active ,Carbohydrate metabolism ,03 medical and health sciences ,Mice ,Internal medicine ,Brown adipose tissue ,medicine ,Myocyte ,Animals ,Humans ,Myocytes, Cardiac ,chemistry.chemical_classification ,Mice, Knockout ,biology ,Insulin ,Myocardium ,Fatty Acids ,Fatty acid ,Endothelial Cells ,General Medicine ,Endothelial stem cell ,Insulin receptor ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Glucose ,chemistry ,Organ Specificity ,biology.protein ,Insulin Resistance ,Research Article - 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.
- Published
- 2017