title: Evidence that chromium modulates cellular cholesterol homeostasis and ABCA1 functionality impaired by hyperinsulinemia--brief report.
abstract: 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+.
  
  
  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.
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University School of Medicine, VanNuys Medical Science Bldg, Rm 308A, Indianapolis, IN 46260, USA.
authors.forename: Whitney
authors.initials: W
authors.lastname: Sealls
authors.forename: Brent A
authors.initials: BA
authors.lastname: Penque
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Elmendorf
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000187:drug effects* / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism; D003980:Diazooxonorleucine / Q000494:pharmacology; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006595:Hexosamines / Q000096:biosynthesis; D006706:Homeostasis; D006946:Hyperinsulinism / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D010848:Picolinic Acids / Q000494:pharmacology*; D021381:Protein Transport; D012265:Ribonucleotides / Q000494:pharmacology; D013997:Time Factors; D020691:rab GTP-Binding Proteins / Q000378:metabolism
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D006595:Hexosamines; D007328:Insulin; D010848:Picolinic Acids; C521976:Rab8 protein, mouse; D012265:Ribonucleotides; D003980:Diazooxonorleucine; D000620:Aminoimidazole Carboxamide; D002784:Cholesterol; D055372:AMP-Activated Protein Kinases; D020691:rab GTP-Binding Proteins; C031143:AICA ribonucleotide; C030614:picolinic acid