Evidence that chromium modulates cellular cholesterol homeostasis and ABCA1 functionality impaired by hyperinsulinemia--brief report

Arterioscler Thromb Vasc Biol. 2011 May;31(5):1139-40. doi: 10.1161/ATVBAHA.110.222158. Epub 2011 Feb 10.


Objective: Trivalent chromium (Cr3+) is an essential micronutrient. Findings since the 1950s suggest that Cr3+ might benefit cholesterol homeostasis. Here we present mechanistic evidence in support of this role of Cr3+.

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 Cr3+. Mechanistically, Cr3+ 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 Cr3+, or inhibition of hexosamine biosynthesis pathway activity, which is known to be elevated by hyperinsulinemia, mimics Cr3+ action.

Conclusions: These findings suggest a mechanism of Cr3+ 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.

Publication types

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

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / drug effects*
  • ATP-Binding Cassette Transporters / metabolism
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Aminoimidazole Carboxamide / analogs & derivatives
  • Aminoimidazole Carboxamide / pharmacology
  • Animals
  • Apolipoprotein A-I / metabolism
  • Cholesterol / metabolism*
  • Cholesterol, HDL / metabolism
  • Diazooxonorleucine / pharmacology
  • Enzyme Activation
  • Enzyme Activators / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Hexosamines / biosynthesis
  • Homeostasis
  • Hyperinsulinism / metabolism*
  • Insulin / metabolism*
  • Mice
  • NIH 3T3 Cells
  • Picolinic Acids / pharmacology*
  • Protein Transport
  • Ribonucleotides / pharmacology
  • Time Factors
  • rab GTP-Binding Proteins / metabolism


  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Apolipoprotein A-I
  • Cholesterol, HDL
  • Enzyme Activators
  • Enzyme Inhibitors
  • Hexosamines
  • Insulin
  • Picolinic Acids
  • Rab8 protein, mouse
  • Ribonucleotides
  • Diazooxonorleucine
  • Aminoimidazole Carboxamide
  • Cholesterol
  • AMP-Activated Protein Kinases
  • rab GTP-Binding Proteins
  • AICA ribonucleotide
  • picolinic acid