Chronic carbon monoxide inhalation has a transient effect to reduce weight gain in mice fed a high fat diet (1107.3)

We recently reported chronic treatment with carbon monoxide (CO) releasing molecules results in prevention of weight gain in mice fed a high fat diet. At present, we sought to determine the effect of chronic CO inhalation on 4 week old lean (Prevent) and 24 week old obese (Reverse) C57BL/6J mice fed a high diet. Two different CO inhalation exposures were used daily for 30 weeks; 28 parts per million (ppm) CO for 2 hours or 200 ppm CO for 1 hour. Body weight, fasted blood glucose and body composition were measured throughout the treatment. Food intake, O2 consumption, CO2 production, motor activity, and body heat production were measured at 28 weeks after the start of the experimental protocol. Compared to high fat diet controls inhalation treatment resulted in prevention and reversal of body weight (Prevent: 36.3gm vs. 42.6gm, p<0.05; Reverse: 45.6gm vs. 52.8gm; p<0.05), fat mass (Prevent: 14.8gm vs. 18.2gm, p<0.05; Reverse: 15.0gm vs. 18.6gm; p<0.05) and, blood glucose (Prevent: 110gm/dl vs. 150gm/dl, p<0.05; Reverse: 124gm/dl vs. 135gm/dl; p<0.05) over the first 10 weeks of treatment, however, this effect was not sustained. No differences were found in any other variables measured. Our results demonstrate that CO inhalation has a transient effect to prevent and reduce body weight which is not sustained in mice fed a high fat diet suggesting chronic CO inhalation therapy is not an effective treatment for long term weight loss. Grant Funding Source : Supported by grants from the NHLBI, PO1HL‐51971, HL088421 (D.E.S.) and 1T32HL105324 (P.A.H).