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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 ALDH1A1. C) Levels of HO-1. D) Levels of PGC1-α. E) Levels of NRF1. F) Levels of UCP1. *= significant from control mice, P<0.05. #= significant from HF + iCORM-A1 treated and control mice, P<0.05. ‡ =P<0.05 as compared to HF + iCORM-A1 treated.
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Figure 6: 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 ALDH1A1. C) Levels of HO-1. D) Levels of PGC1-α. E) Levels of NRF1. F) Levels of UCP1. *= significant from control mice, P<0.05. #= significant from HF + iCORM-A1 treated and control mice, P<0.05. ‡ =P<0.05 as compared to HF + iCORM-A1 treated.

Mentions: In samples of epidydimal fat, chronic CORM-A1 treatment increased levels of peroxisomal proliferating activating receptor- γ coactivator (PGC-1α) and nuclear respiratory factor-1 (NRF-1) which are considered markers of mitochondrial biogenesis (Figure 6A, D, E). Levels of uncoupling protein-1 (UCP1) were also increased in epidydimal fat of CORM-A1 treated mice (Figure 6A and F). The levels of heme oxygenase-1 (HO-1) were increased in the epidydimal fat of both groups of mice fed a high fat diet as compared with control mice on a normal fat diet (Figure 6A and C).


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 ALDH1A1. C) Levels of HO-1. D) Levels of PGC1-α. E) Levels of NRF1. F) Levels of UCP1. *= significant from control mice, P<0.05. #= significant from HF + iCORM-A1 treated and control mice, P<0.05. ‡ =P<0.05 as compared to HF + iCORM-A1 treated.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 6: 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 ALDH1A1. C) Levels of HO-1. D) Levels of PGC1-α. E) Levels of NRF1. F) Levels of UCP1. *= significant from control mice, P<0.05. #= significant from HF + iCORM-A1 treated and control mice, P<0.05. ‡ =P<0.05 as compared to HF + iCORM-A1 treated.
Mentions: In samples of epidydimal fat, chronic CORM-A1 treatment increased levels of peroxisomal proliferating activating receptor- γ coactivator (PGC-1α) and nuclear respiratory factor-1 (NRF-1) which are considered markers of mitochondrial biogenesis (Figure 6A, D, E). Levels of uncoupling protein-1 (UCP1) were also increased in epidydimal fat of CORM-A1 treated mice (Figure 6A and F). The levels of heme oxygenase-1 (HO-1) were increased in the epidydimal fat of both groups of mice fed a high fat diet as compared with control mice on a normal fat diet (Figure 6A and C).

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