Endothelial cell CD36 optimizes tissue fatty acid uptake

J Clin Invest. 2018 Oct 1;128(10):4329-4342. doi: 10.1172/JCI99315. Epub 2018 Jul 26.

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.

Keywords: Endocrinology; Glucose metabolism; Insulin signaling; Lipoproteins; Metabolism.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biological Transport, Active / genetics
  • CD36 Antigens / genetics
  • CD36 Antigens / metabolism*
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology
  • Fatty Acids / genetics
  • Fatty Acids / metabolism*
  • Glucose / genetics
  • Glucose / metabolism
  • Humans
  • Insulin Resistance
  • Mice
  • Mice, Knockout
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • Organ Specificity

Substances

  • CD36 Antigens
  • CD36 protein, human
  • Cd36 protein, mouse
  • Fatty Acids
  • Glucose