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Chronic Carbon Monoxide Treatment Attenuates the Development of Obesity and Remodels Adipocytes in Mice Fed a High Fat Diet
Author(s) -
Hosick Peter Andrew,
Al Amoudi Abdulhadi A,
Storm Megan V,
Gousset Monette U,
Pruett Brandon E,
Gray Will,
Stout Jacob,
Stec David E
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1154.4
Subject(s) - medicine , endocrinology , mitochondrial biogenesis , adipose tissue , heme oxygenase , chemistry , obesity , metabolite , mitochondrion , heme , biochemistry , enzyme
Several studies have demonstrated chronic induction of heme oxygenase‐1 can attenuate the development of obesity; yet, the specific role of its metabolite, carbon monoxide (CO), in mediating this response is not known. The objective of this study was to test the hypothesis that increases in CO mediate the effects of HO‐1 induction in obesity. Mice fed a 60% fat diet were treated with the CO releasing compound, CORM‐A1 (5 mg/kg body weight, i.p.) or the inactive compound iCORM‐A1 (iCO) every 48‐hours for 30 weeks. At 30 weeks of treatment body weights of mice receiving CO injections were significantly reduced compared to iCO treated mice (38 ± 1 vs. 43± 1 grams; p<0.05, n=9/grp). Oxygen consumption measured at 27 weeks of treatment was significantly increased in CO treated mice versus iCO treated mice (96 ± 3 vs. 81 ± 5 ml/LBM/min; p<0.05, n=9/grp). CO treatment decreased the size of epididymal adipocytes compared to iCO treatment (2911 ± 343 vs. 6067 ± 339 μm 2 ; p<0.05, n=3/grp). Chronic CO treatment increased levels of proteins involved in mitochondrial biogenesis such as: NRF‐1, PGC‐1α, Nrf‐2, and UCP‐1 (p<0.05) in adipocytes. In conclusion, our results show chronic CO treatment promotes weight loss and enhances metabolism via up‐regulation of mitochondrial biogenesis, mitochondrial uncoupling, and the remodeling of white adipose tissue thus establishing low level chronic CO treatment as a novel anti‐obesity treatment.