Inhalation of carbon monoxide is ineffective as a long-term therapy to reduce obesity in mice fed a high fat diet

Abstract

Background: Previous studies have demonstrated that induction of heme oxygenase-1 results in weight loss in several rodent models of obesity. However, the specific role of the heme oxygenase-1 metabolite, carbon monoxide (CO), in this response has yet to be established. We recently reported that chronic treatment with CO releasing molecules results in prevention of weight gain in mice fed a high fat diet. In the present study, we sought to determine the effect of chronic CO inhalation on the development and reversal of high fat diet induced obesity.

Results: CO inhalation at both levels initially resulted in a prevention and reversal of body weight and fat mass over the first 10 weeks of treatment, however, this effect was not sustained. CO inhalation in the prevention groups also had an early effect to lower fasting blood glucose but this effect also was not sustained.

Conclusions: Our results demonstrate that CO inhalation has a transient effect to prevent and reduce body weight which is not sustained chronically in mice fed a high fat diet. These results suggest that chronic CO inhalation therapy is not an effective treatment to induce long term weight loss.

Keywords: Heme oxygenase; Insulin resistance; Metabolism; Obesity; Type II diabetes.

Figure 1

Carboxyhemoglobin percentage before and following inhalation of CO at 200 ppm for 1 hr (n = 4) or 20 ppm for 2 hrs (n = 4). * = significant from pre value, p < 0.05.

Figure 2

Effect of chronic CO inhalation on: (A) obesity prevention body weight measured weekly, (B) obesity prevention body fat percentage as measured by echo-MRI, (C) obesity reversal body weight measured weekly, (D) obesity reversal body fat percentage as measured by echo-MRI. * = significant from HF Control, p < 0.05. # = significant from all other groups, p < 0.05.

Figure 3

Effect of chronic CO inhalation on fasting blood glucose in the: (A) Prevention groups, (B) Reversal groups. * = significant from HF Control, p < 0.05. # = significant from all other groups, p < 0.05.

Figure 4

Representative Western blots from epidydmal fat tissues of chronic CO inhalation for the reversal of obesity from high fat diet (HFD) control, HFD 28 ppm CO, HFD 200 ppm CO mice. A) Representative blots. B) Levels of HO-1. C) Levels of PGC1-α. D) Levels of NRF1. E) Levels of ALDH1A1. * = significant from all other groups, p < 0.05. MWM = molecular weight marker.

Figure 5

Representative Western blots from epidydmal fat tissues of chronic CO inhalation for the prevention of obesity from normal fat control, high fat diet (HFD) control, HFD 28 ppm CO, HFD 200 ppm CO mice. A) Representative blots. B) Levels of HO-1. C) Levels of PGC1-α. D) Levels of NRF1. E) Levels of ALDH1A1. * = significant from all other groups, p < 0.05. # = significant from HF Control mice, p < 0.05. MWM = molecular weight marker.