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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

Effect of CORM-A1 treatment on: A) fat mass as measured by echo-MRI, B) lean mass as measured by echo-MRI, C) fat pad weights measured at the end of the 30 week experimental protocol 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 HF treated mice, P<0.05. #= significant from iCORM-A1 treated mice, P<0.05.
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Figure 2: Effect of CORM-A1 treatment on: A) fat mass as measured by echo-MRI, B) lean mass as measured by echo-MRI, C) fat pad weights measured at the end of the 30 week experimental protocol 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 HF treated mice, P<0.05. #= significant from iCORM-A1 treated mice, P<0.05.

Mentions: High fat feeding in mice resulted in significant elevations in body weight as compared to mice fed standard chow by week 10 of the study. CORM-A1 treatment resulted in reduced body weight starting at week 19 and remained lower in the CORM-A1 treated mice as compared to the iCORM-A1, which is the inactive form of the CO donor, treated mice throughout the duration of the study (Figure 1). Fat mass as measured by echo-MRI was increased in both groups of high fat fed mice as compared to control mice fed a standard chow. However, fat mass was significantly decreased in CORM-A1 as compared to iCORM-A1 treated mice at 12, 18, and 24 weeks (Figure 2A). No differences in lean mass were detected between the groups at 12, 18, 24 or 30 weeks of age (Figure 2B). Fat pad weight measured at the end of the study was impacted by chronic treatment of CORM-A1. Epididymal fat was significantly increased in iCORM-A1 treated mice as compared to both CORM-A1 and control mice (Figure 2C). Visceral fat was increased in both groups fed a high fat diet as compared to control mice but visceral fat weight was significantly higher in iCORM-A1 treated versus CORM-A1 treated mice (Figure 2C). Total fat was also increased in both groups fed a high fat diet as compared to control mice but the total amount of fat was significantly less in the CORM-A1 as compared to the iCORM-A1 treated mice (Figure 2C).


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)

Effect of CORM-A1 treatment on: A) fat mass as measured by echo-MRI, B) lean mass as measured by echo-MRI, C) fat pad weights measured at the end of the 30 week experimental protocol 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 HF treated mice, P<0.05. #= significant from iCORM-A1 treated mice, P<0.05.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3760985&req=5

Figure 2: Effect of CORM-A1 treatment on: A) fat mass as measured by echo-MRI, B) lean mass as measured by echo-MRI, C) fat pad weights measured at the end of the 30 week experimental protocol 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 HF treated mice, P<0.05. #= significant from iCORM-A1 treated mice, P<0.05.
Mentions: High fat feeding in mice resulted in significant elevations in body weight as compared to mice fed standard chow by week 10 of the study. CORM-A1 treatment resulted in reduced body weight starting at week 19 and remained lower in the CORM-A1 treated mice as compared to the iCORM-A1, which is the inactive form of the CO donor, treated mice throughout the duration of the study (Figure 1). Fat mass as measured by echo-MRI was increased in both groups of high fat fed mice as compared to control mice fed a standard chow. However, fat mass was significantly decreased in CORM-A1 as compared to iCORM-A1 treated mice at 12, 18, and 24 weeks (Figure 2A). No differences in lean mass were detected between the groups at 12, 18, 24 or 30 weeks of age (Figure 2B). Fat pad weight measured at the end of the study was impacted by chronic treatment of CORM-A1. Epididymal fat was significantly increased in iCORM-A1 treated mice as compared to both CORM-A1 and control mice (Figure 2C). Visceral fat was increased in both groups fed a high fat diet as compared to control mice but visceral fat weight was significantly higher in iCORM-A1 treated versus CORM-A1 treated mice (Figure 2C). Total fat was also increased in both groups fed a high fat diet as compared to control mice but the total amount of fat was significantly less in the CORM-A1 as compared to the iCORM-A1 treated mice (Figure 2C).

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