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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

Effects of chronic CORM-A1 treatment on A) oxygen consumption (VO2), B) carbon dioxide production (VCO2), C) heat production, D) motor activity and E) food intake in control (n=4), high fat (HF) + CORM-A1 (n=9), and high fat (HF) + inactive CORM-A1 (iCORM-A1, n=9) treated mice. *= significant from control and HF + iCORM-A1 treated. † = significant from high fat mice, P<0.05.
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Figure 4: Effects of chronic CORM-A1 treatment on A) oxygen consumption (VO2), B) carbon dioxide production (VCO2), C) heat production, D) motor activity and E) food intake in control (n=4), high fat (HF) + CORM-A1 (n=9), and high fat (HF) + inactive CORM-A1 (iCORM-A1, n=9) treated mice. *= significant from control and HF + iCORM-A1 treated. † = significant from high fat mice, P<0.05.

Mentions: In order to determine the effect of chronic CORM-A1 on metabolism, mice were placed in metabolic chambers at 28 weeks of treatment for measurement of oxygen consumption, carbon dioxide production, heat production and activity. Oxygen consumption when normalized to the lean body weight as measured by echo-MRI was significantly elevated in the CORM-A1 treated mice on the high fat diet as compared to both iCORM-A1 treated and control mice fed a standard diet (Figure 4A). Carbon dioxide production when normalized to lean body weight was increased in the CORM-A1 treated mice as compared to both iCORM-A1 and control mice but this increase did not achieve statistical significance (Figure 4B). Heat production was significantly increased in CORM-A1 treated mice as compared to both iCORM-A1 and control mice (Figure 4C). High fat feeding resulted in a significant decrease in activity as compared to control mice which was not reversed by CORM-A1 treatment (Figure 4D). Measured over a 5 day period at 29 weeks after commencement of injections, food intake was not different between any of the groups; however, the caloric intake of the mice fed a high fat diet was higher than that of the mice fed a normal fat diet (Figure 4E).


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)

Effects of chronic CORM-A1 treatment on A) oxygen consumption (VO2), B) carbon dioxide production (VCO2), C) heat production, D) motor activity and E) food intake in control (n=4), high fat (HF) + CORM-A1 (n=9), and high fat (HF) + inactive CORM-A1 (iCORM-A1, n=9) treated mice. *= significant from control and HF + iCORM-A1 treated. † = significant from high fat mice, P<0.05.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: Effects of chronic CORM-A1 treatment on A) oxygen consumption (VO2), B) carbon dioxide production (VCO2), C) heat production, D) motor activity and E) food intake in control (n=4), high fat (HF) + CORM-A1 (n=9), and high fat (HF) + inactive CORM-A1 (iCORM-A1, n=9) treated mice. *= significant from control and HF + iCORM-A1 treated. † = significant from high fat mice, P<0.05.
Mentions: In order to determine the effect of chronic CORM-A1 on metabolism, mice were placed in metabolic chambers at 28 weeks of treatment for measurement of oxygen consumption, carbon dioxide production, heat production and activity. Oxygen consumption when normalized to the lean body weight as measured by echo-MRI was significantly elevated in the CORM-A1 treated mice on the high fat diet as compared to both iCORM-A1 treated and control mice fed a standard diet (Figure 4A). Carbon dioxide production when normalized to lean body weight was increased in the CORM-A1 treated mice as compared to both iCORM-A1 and control mice but this increase did not achieve statistical significance (Figure 4B). Heat production was significantly increased in CORM-A1 treated mice as compared to both iCORM-A1 and control mice (Figure 4C). High fat feeding resulted in a significant decrease in activity as compared to control mice which was not reversed by CORM-A1 treatment (Figure 4D). Measured over a 5 day period at 29 weeks after commencement of injections, food intake was not different between any of the groups; however, the caloric intake of the mice fed a high fat diet was higher than that of the mice fed a normal fat diet (Figure 4E).

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