Lipid-induced insulin resistance is associated with increased monocyte expression of scavenger receptor CD36 and internalization of oxidized LDL

Obesity (Silver Spring). 2009 Dec;17(12):2142-8. doi: 10.1038/oby.2009.179. Epub 2009 Jun 11.

Abstract

Elevated free fatty acids (FFAs) contribute to the development of insulin resistance, type 2 diabetes mellitus (T2DM), and may be atherogenic. We tested the relationship among lipid-induced insulin resistance, endothelial dysfunction, and monocyte capacity to form foam cells through scavenger receptor A (SRA) and CD36. Ten healthy subjects underwent 24-h infusion of Intralipid/heparin and saline (0.5 ml/min) on two separate occasions followed by brachial artery reactivity testing and a euglycemic hyperinsulinemic (80 mU/(kg.min)) clamp study to determine insulin sensitivity. Isolation of blood monocytes was performed 24 h after infusion. Surface expression and function of CD36 and SRA to take up oxidized low-density lipoprotein (oxLDL) was determined by flow cytometry and quantitative confocal imaging. Lipid infusion resulted in a twofold increase in serum FFA levels, reduced whole-body glucose disposal by approximately 20% (P < 0.05), and possibly impaired endothelial-dependent vasodilation (P = 0.1). Blood monocytes obtained during lipid infusion demonstrated a approximately 25% increase in cell surface expression of CD36 (P < 0.05) but no change in SRA expression. Enhanced CD36 expression was associated with a 50% increase in internalization of oxLDL (P < 0.05). The increase in CD36 surface expression during lipid infusion correlated inversely with glucose disposal (P < 0.05) and not with FFA levels or brachial artery dilation. These data support a role for FFAs in induction of insulin resistance and provide a link to atherogenic mechanisms mediated by expression of scavenger receptor CD36.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anticoagulants / administration & dosage
  • Anticoagulants / pharmacology
  • Brachial Artery / drug effects
  • CD36 Antigens / blood*
  • Endothelium
  • Fat Emulsions, Intravenous / administration & dosage
  • Fat Emulsions, Intravenous / pharmacology*
  • Fatty Acids, Nonesterified / blood*
  • Female
  • Flow Cytometry
  • Foam Cells / metabolism
  • Glucose / metabolism
  • Heparin / administration & dosage
  • Heparin / pharmacology
  • Humans
  • Insulin Resistance / immunology
  • Insulin Resistance / physiology*
  • Lipoproteins, LDL / metabolism*
  • Male
  • Microscopy, Confocal
  • Middle Aged
  • Monocytes / metabolism*
  • Reference Values
  • Scavenger Receptors, Class A / metabolism*
  • Vasodilation / drug effects

Substances

  • Anticoagulants
  • CD36 Antigens
  • Fat Emulsions, Intravenous
  • Fatty Acids, Nonesterified
  • Lipoproteins, LDL
  • Scavenger Receptors, Class A
  • oxidized low density lipoprotein
  • Heparin
  • Glucose