title: Chronic carbon monoxide treatment attenuates development of obesity and remodels adipocytes in mice fed a high-fat diet.
abstract: OBJECTIVE
  Induction of heme oxygenase-1 (HO-1) has been demonstrated to result in chronic weight loss in several rodent models of obesity. However, the specific contribution of the HO metabolite, carbon monoxide (CO) to this response remains unknown. In this study, we determined the effect of chronic low level administration of a specific CO donor on the progression of obesity and its effects on metabolism and adipocyte biology in mice fed a high-fat diet.
  
  
  METHODS
  Experiments were performed on C57BL/6J mice fed a high-fat diet (60%) from 4 weeks until 30 weeks of age. Mice were administered either the CO donor, carbon monoxide releasing molecules (CORM)-A1 (5 mg kg(-1), intraperitoneally every other day) or the inactive form of the drug (iCORM-A1). Body weights were measured weekly and fasted blood glucose, insulin as well as body composition were measured every 6 weeks. Food intake, O2 consumption, CO2 production, activity and body heat production were measured at 28 weeks after start of the experimental protocol.
  
  
  RESULTS
  Chronic CORM-A1 attenuated the development of high fat induced obesity from 18 weeks until the end of the study. Chronic CORM-A1 treatment in mice fed a high-fat diet resulted in significant decreases in fasted blood glucose, insulin and body fat and increased O2 consumption and heat production as compared with mice treated with iCORM-A1. Chronic CORM-A1 treatment also resulted in a significant decrease in adipocyte size and an increase in adipocyte number and in NRF-1, PGC-1α and UCP1 protein levels in epidydmal fat.
  
  
  CONCLUSIONS
  Our results demonstrate that chronic CO treatment prevents the development of high-fat diet induced obesity via stimulation of metabolism and remodeling of adipocytes.
authors.affiliation: Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Hosick
authors.affiliation: Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: AlAmodi
authors.affiliation: Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: M V
authors.initials: MV
authors.lastname: Storm
authors.affiliation: Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: M U
authors.initials: MU
authors.lastname: Gousset
authors.affiliation: Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: B E
authors.initials: BE
authors.lastname: Pruett
authors.affiliation: Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: W
authors.initials: W
authors.lastname: Gray
authors.affiliation: Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: J
authors.initials: J
authors.lastname: Stout
authors.affiliation: Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Stec
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D001880:Boranes / Q000494:pharmacology*; D002248:Carbon Monoxide / Q000494:pharmacology; D002254:Carbonates / Q000494:pharmacology*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004435:Eating; D051547:Heme Oxygenase-1 / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D015854:Up-Regulation; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D001786:Blood Glucose; D001880:Boranes; D002254:Carbonates; C503854:sodium boranocarbonate; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1