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

Hosick PA, AlAmodi AA, Storm MV, Gousset MU, Pruett BE, Gray W, Stout J, Stec DE - Int J Obes (Lond) (2013)

Bottom Line: Body weights were measured weekly and fasted blood glucose, insulin as well as body composition were measured every 6 weeks.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, MS, USA.

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, 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.

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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Related in: MedlinePlus

Representative hematoxylin and eosin (H &E) staining of epidydmal fat tissues from A) control, B) high fat (HF) + CORM-A1, and C) high fat (HF) + iCORM-A1 treated mice. D) adipocyte number from the different treatment groups (n=3 per group). E) adipocyte size of the different treatment groups (n=3 per group). *= significant from HF treated mice, P<0.05. #= significant from iCORM-A1 treated mice, P<0.05.
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Figure 5: Representative hematoxylin and eosin (H &E) staining of epidydmal fat tissues from A) control, B) high fat (HF) + CORM-A1, and C) high fat (HF) + iCORM-A1 treated mice. D) adipocyte number from the different treatment groups (n=3 per group). E) adipocyte size of the different treatment groups (n=3 per group). *= significant from HF treated mice, P<0.05. #= significant from iCORM-A1 treated mice, P<0.05.

Mentions: The effect of chronic CORM-A1 treatment on adipocyte number and morphology was determined in sections of epididymal fat obtained at the end of the experimental protocol. High fat diet resulted in a decrease in number and an increase in epididymal adipocyte size as compared to mice fed a standard diet (Figure 5). CORM-A1 treatment resulted in a significant increase in epididymal adipocyte number as compared to iCORM-A1 treated mice (Figure 5D). CORM-A1 also resulted in a significant decrease in epididymal adipocyte size as compared to iCORM-A1 treated mice (Figure 5E). No significant differences in adipocyte number or size were detected in the subcutaneous fat between any of the groups (Supplementary Figure 1).


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

Hosick PA, AlAmodi AA, Storm MV, Gousset MU, Pruett BE, Gray W, Stout J, Stec DE - Int J Obes (Lond) (2013)

Representative hematoxylin and eosin (H &E) staining of epidydmal fat tissues from A) control, B) high fat (HF) + CORM-A1, and C) high fat (HF) + iCORM-A1 treated mice. D) adipocyte number from the different treatment groups (n=3 per group). E) adipocyte size of the different treatment groups (n=3 per group). *= significant from HF treated mice, P<0.05. #= significant from iCORM-A1 treated mice, P<0.05.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3760985&req=5

Figure 5: Representative hematoxylin and eosin (H &E) staining of epidydmal fat tissues from A) control, B) high fat (HF) + CORM-A1, and C) high fat (HF) + iCORM-A1 treated mice. D) adipocyte number from the different treatment groups (n=3 per group). E) adipocyte size of the different treatment groups (n=3 per group). *= significant from HF treated mice, P<0.05. #= significant from iCORM-A1 treated mice, P<0.05.
Mentions: The effect of chronic CORM-A1 treatment on adipocyte number and morphology was determined in sections of epididymal fat obtained at the end of the experimental protocol. High fat diet resulted in a decrease in number and an increase in epididymal adipocyte size as compared to mice fed a standard diet (Figure 5). CORM-A1 treatment resulted in a significant increase in epididymal adipocyte number as compared to iCORM-A1 treated mice (Figure 5D). CORM-A1 also resulted in a significant decrease in epididymal adipocyte size as compared to iCORM-A1 treated mice (Figure 5E). No significant differences in adipocyte number or size were detected in the subcutaneous fat between any of the groups (Supplementary Figure 1).

Bottom Line: Body weights were measured weekly and fasted blood glucose, insulin as well as body composition were measured every 6 weeks.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, MS, USA.

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, 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.

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.

Show MeSH
Related in: MedlinePlus