Cell Biology/Signaling Evidence That Chromium Modulates Cellular Cholesterol Homeostasis and ABCA1 Functionality Impaired by Hyperinsulinemia—Brief Report

Objective—Trivalent chromium (Cr ) is an essential micronutrient. Findings since the 1950s suggest that Cr might benefit cholesterol homeostasis. Here we present mechanistic evidence in support of this role of Cr . Methods and Results—High-density lipoprotein cholesterol generation in 3T3-L1 adipocytes, which are rendered ineffective by the hyperinsulinemia that is known to accompany disorders of lipid metabolism, was corrected by Cr . Mechanistically, Cr reversed hyperinsulinemia-induced cellular cholesterol accrual and associated defects in cholesterol transporter ATP-binding cassette transporter-A1 trafficking and apolipoprotein A1–mediated cholesterol efflux. Moreover, direct activation of AMP-activated protein kinase, which is known to be activated by Cr , or inhibition of hexosamine biosynthesis pathway activity, which is known to be elevated by hyperinsulinemia, mimics Cr action. Conclusion—These findings suggest a mechanism of Cr action that fits with long-standing claims of its role in cholesterol homeostasis. Furthermore, these data imply a mechanistic basis for the coexistence of dyslipidemia with hyperinsulinemia. (Arterioscler Thromb Vasc Biol. 2011;31:1139-1140.)