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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 Western blots from epidydmal fat tissues from control (n=4), high fat (HF) + CORM-A1 (n=6), and high fat (HF) + iCORM-A1 treated mice (n=6). A) Representative blots. B) Levels of HIF-1α. C) Levels of VEGF. D) Levels of collagen type I. E) Levels of collagen type III. F) Levels of fibronectin. *= significant from control mice, P<0.05. #= significant from HF + iCORM-A1 treated and control mice, P<0.05.
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Figure 8: Representative Western blots from epidydmal fat tissues from control (n=4), high fat (HF) + CORM-A1 (n=6), and high fat (HF) + iCORM-A1 treated mice (n=6). A) Representative blots. B) Levels of HIF-1α. C) Levels of VEGF. D) Levels of collagen type I. E) Levels of collagen type III. F) Levels of fibronectin. *= significant from control mice, P<0.05. #= significant from HF + iCORM-A1 treated and control mice, P<0.05.

Mentions: The levels of hypoxia inducible factor 1-α (HIF-1α) as well as the levels of vascular endothelial derived growth factor (VEGF) were measure in samples of epidydmal fat from mice in each treatment groups. HIF-1α levels were significantly elevated in the epidydmal fat of CORM-A1 mice as compared to both iCORM-A1 and control mice (Figure 8A &B). VEGF levels were also significantly increased in CORM-A1 treated mice as compared to both iCORM-A1 treated mice on a high fat diet and control mice on a normal fat diet (Figure 8A &C). In order to further address adipocyte remodeling, the levels of collagen I and III as well as fibronectin levels were measured in samples of epidydmal fat from mice in each treatment group. No differences in collagen I or III levels were detected between the groups (Figure 8A, D &E). Fibronectin levels were decreased by high fat diet treatment and CORM-A1 treatment had no effect on this response (Figure 8A & F).


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 Western blots from epidydmal fat tissues from control (n=4), high fat (HF) + CORM-A1 (n=6), and high fat (HF) + iCORM-A1 treated mice (n=6). A) Representative blots. B) Levels of HIF-1α. C) Levels of VEGF. D) Levels of collagen type I. E) Levels of collagen type III. F) Levels of fibronectin. *= significant from control mice, P<0.05. #= significant from HF + iCORM-A1 treated and control mice, P<0.05.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 8: Representative Western blots from epidydmal fat tissues from control (n=4), high fat (HF) + CORM-A1 (n=6), and high fat (HF) + iCORM-A1 treated mice (n=6). A) Representative blots. B) Levels of HIF-1α. C) Levels of VEGF. D) Levels of collagen type I. E) Levels of collagen type III. F) Levels of fibronectin. *= significant from control mice, P<0.05. #= significant from HF + iCORM-A1 treated and control mice, P<0.05.
Mentions: The levels of hypoxia inducible factor 1-α (HIF-1α) as well as the levels of vascular endothelial derived growth factor (VEGF) were measure in samples of epidydmal fat from mice in each treatment groups. HIF-1α levels were significantly elevated in the epidydmal fat of CORM-A1 mice as compared to both iCORM-A1 and control mice (Figure 8A &B). VEGF levels were also significantly increased in CORM-A1 treated mice as compared to both iCORM-A1 treated mice on a high fat diet and control mice on a normal fat diet (Figure 8A &C). In order to further address adipocyte remodeling, the levels of collagen I and III as well as fibronectin levels were measured in samples of epidydmal fat from mice in each treatment group. No differences in collagen I or III levels were detected between the groups (Figure 8A, D &E). Fibronectin levels were decreased by high fat diet treatment and CORM-A1 treatment had no effect on this response (Figure 8A & F).

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