Abstract 217: Chronic Treatment with Carbon Monoxide Releasing Molecule Reverses Dietary Induced Obesity in Mice

We have recently demonstrated that chronic, low level treatment with carbon monoxide releasing molecules (CORMs) prevents the development of obesity in response to a high fat diet. The objective of this study was to test the hypothesis that chronic, low level treatment with CORM can reverse established obesity via a mechanism independent of food intake. This hypothesis was tested by treating 24 week old DIO C57BL6/J mice with a low level of the CO releasing compound, CORM-A1 (5 mg/kg body weight, i.p.; n=4) or the inactive compound iCORM-A1 (n=6) every 48-hours for 30 weeks while maintaining a high fat (60%) diet. Initial body weights (BW) were not different between the groups; however, at 30 weeks of treatment, CORM-A1 significantly reduced body weight as compared to iCORM-A1 (32.7±2.9 g (62% of initial BW) vs. 52.1±13.2 g; pLBM /min vs.70.4±16.6 mL/kg LBM /min; p=0.07). However, weight loss in CORM-A1 treated mice was independent of differences in motor activity (4665±2396 cm vs. 5339±3325 cm, p=0.81) and food intake (3.1±0.2 g/day vs. 3.5±0.1 g/day; p=0.1). These results demonstrate that chronic, low level treatment with a CO donor at levels which do not raise blood carboxyhemoglobin levels reverses established obesity in mice fed a high fat diet through a mechanism independent of food intake. Our results suggest that chronic, low level treatment with CO releasing compounds may be a novel therapy for the reversal of obesity. This work was supported by grants from the NHLBI, PO1HL-51971, HL088421 and 1T32HL105324.