Faculty Collaboration Database

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

Date

06/13/2009

Pubmed ID

19521352

Pubmed Central ID

PMC2836489

DOI

10.1038/oby.2009.179

Scopus ID

2-s2.0-72449157475 (requires institutional sign-in at Scopus site)   51 Citations

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.

Author List

Kashyap SR, Ioachimescu AG, Gornik HL, Gopan T, Davidson MB, Makdissi A, Major J, Febbraio M, Silverstein RL

Authors

Adriana G. Ioachimescu MD, PhD Professor in the Medicine department at Medical College of Wisconsin
Roy L. Silverstein MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Anticoagulants
Brachial Artery
CD36 Antigens
Endothelium
Fat Emulsions, Intravenous
Fatty Acids, Nonesterified
Female
Flow Cytometry
Foam Cells
Glucose
Heparin
Humans
Insulin Resistance
Lipoproteins, LDL
Male
Microscopy, Confocal
Middle Aged
Monocytes
Reference Values
Scavenger Receptors, Class A
Vasodilation