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Lipid‐induced Insulin Resistance Is Associated With Increased Monocyte Expression of Scavenger Receptor CD36 and Internalization of Oxidized LDL
Author(s) -
Kashyap Sangeeta R.,
Ioachimescu Adriana G.,
Gornik Heather L.,
Gopan Thottathil,
Davidson Michael B.,
Makdissi Antonie,
Major Jennifer,
Febbraio Maria,
Silverstein Roy L.
Publication year - 2009
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1038/oby.2009.179
Subject(s) - cd36 , scavenger receptor , medicine , endocrinology , insulin resistance , insulin , monocyte , lipoprotein , chemistry , receptor , cholesterol
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 ∼20% ( P < 0.05), and possibly impaired endothelial‐dependent vasodilation ( P = 0.1). Blood monocytes obtained during lipid infusion demonstrated a ∼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.