Chronic carbon monoxide treatment attenuates development of obesity and remodels adipocytes in mice fed a high-fat diet

Peter Hosick, A. A. Alamodi, M. V. Storm, M. U. Gousset, B. E. Pruett, W. Gray, J. Stout, D. E. Stec

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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.Design: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, O 2 consumption, CO 2 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 O 2 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-1 and UCP1 protein levels in epidydmal fat.Conclusion:Our results demonstrate that chronic CO treatment prevents the development of high-fat diet induced obesity via stimulation of metabolism and remodeling of adipocytes.

Original languageEnglish
Pages (from-to)132-139
Number of pages8
JournalInternational Journal of Obesity
Volume38
Issue number1
DOIs
StatePublished - 1 Jan 2014

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High Fat Diet
Carbon Monoxide
Adipocytes
Obesity
Thermogenesis
Blood Glucose
Fats
Insulin
Heme Oxygenase-1
Body Composition
Inbred C57BL Mouse
Adipose Tissue
Weight Loss
Rodentia
Eating
Body Weight

Keywords

  • diabetes
  • heme oxygenase
  • insulin resistance
  • metabolism
  • oxygen consumption

Cite this

Hosick, Peter ; Alamodi, A. A. ; Storm, M. V. ; Gousset, M. U. ; Pruett, B. E. ; Gray, W. ; Stout, J. ; Stec, D. E. / Chronic carbon monoxide treatment attenuates development of obesity and remodels adipocytes in mice fed a high-fat diet. In: International Journal of Obesity. 2014 ; Vol. 38, No. 1. pp. 132-139.
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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.Design: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, O 2 consumption, CO 2 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 O 2 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-1 and UCP1 protein levels in epidydmal fat.Conclusion:Our results demonstrate that chronic CO treatment prevents the development of high-fat diet induced obesity via stimulation of metabolism and remodeling of adipocytes.",
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Chronic carbon monoxide treatment attenuates development of obesity and remodels adipocytes in mice fed a high-fat diet. / Hosick, Peter; Alamodi, A. A.; Storm, M. V.; Gousset, M. U.; Pruett, B. E.; Gray, W.; Stout, J.; Stec, D. E.

In: International Journal of Obesity, Vol. 38, No. 1, 01.01.2014, p. 132-139.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Chronic carbon monoxide treatment attenuates development of obesity and remodels adipocytes in mice fed a high-fat diet

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AU - Alamodi, A. A.

AU - Storm, M. V.

AU - Gousset, M. U.

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AU - Stout, J.

AU - Stec, D. E.

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N2 - 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.Design: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, O 2 consumption, CO 2 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 O 2 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-1 and UCP1 protein levels in epidydmal fat.Conclusion:Our results demonstrate that chronic CO treatment prevents the development of high-fat diet induced obesity via stimulation of metabolism and remodeling of adipocytes.

AB - 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.Design: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, O 2 consumption, CO 2 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 O 2 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-1 and UCP1 protein levels in epidydmal fat.Conclusion:Our results demonstrate that chronic CO treatment prevents the development of high-fat diet induced obesity via stimulation of metabolism and remodeling of adipocytes.

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KW - heme oxygenase

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