Development of carbon monoxide-releasing molecules conjugated to polysaccharides (glyco-CORMs) for delivering CO during obesity

An orally active carbon monoxide-releasing molecule enhances beneficial gut microbial species to combat obesity in mice

“…CORM-401 markedly attenuated HFD-induced obesity as evidenced by a reduced body weight gain, which was very similar to that of mice under a standard diet (SD) ( Fig. 1 A and B; Supplementary Figure S1A), confirming previously reported data [ 6 , 20 ]. Notably, the increase in body weight under HFD was not affected by MnS administration, implicating CO as the main responsible for the beneficial effects mediated by CORM-401 ( Fig.…”

“…Administration of CORM-401 to mice has been previously shown to result in temporal increases in blood carboxyhemoglobin (COHb) levels and accumulation of CO in the adipose tissue [ 6 ]. Due to the pharmacokinetic properties of the compound and the presence of several CO-binding targets in organs/tissues, we assumed that after treatment, CO liberated by CORM-401 will also distribute in different body compartments [ 20 ]. We therefore examined CO accumulation over a time course of 48 h in blood, major tissues and organs of mice receiving CORM-401 ( Fig.…”

“…1 E). We measured CO spectrophotometrically using the sensitive CO scavenger hemoCD), which extracts and avidly traps CO from homogenized tissues with extremely high affinity [ 6 , 20 , 25 ]. We found a significant and similar increase in COHb in SD and HFD mice treated with CORM-401 after 1 h, which decreased thereafter to control levels by 24 and 48 h ( Fig.…”

“…Mice were fed a standard diet (SD) or a high fat diet (HFD) and randomly assigned to 4 groups (n = 10 per group): (1) SD; (2) HFD; (3) HFD administered with CORM-401 (HFD-CO) and (4) HFD administered with the negative control (MnS). CORM-401 (30 mg/kg = 0.09 mmol/kg) and MnS (0.09 mmol/kg) were orally administered three times a week for 14 weeks as previously described [ 6 , 20 ]. Body weight was recorded weekly and food consumption was assessed at weeks 7 and 14.…”

“…The final solutions were treated again with 1–2 mg Na 2 S 2 O 4 before absorbance spectra were recorded. The amount of CO was calculated based on the reported extinction coefficients for hemoCD1 at 422 and 434 nm and expressed over mg of tissue/faeces [ 19 , 20 ].…”