Celastrol attenuates HFD-induced obesity and improves metabolic function independent of adiponectin signaling.

Abstract

Backgound: Celastrol, a leptin sensitiser, has been shown to inhibit food intake and reduce body weight in diet-induced obese mice, making it a potential treatment for obesity and metabolic diseases. Adiponectin signalling has been reported to play an important role in the treatment of obesity, inflammation, and non-alcoholic fatty liver disease.

Materials and methods: Wild-type (WT) and AdipoR1 knockout (AdipoR1^-/-) mice were placed on a chow diet or a high-fat diet (HFD) and several metabolic parameters were measured. Celastrol was then administered to the HFD-induced mice and the response of WT and AdipoR1^-/- mice to celastrol in terms of body weight, blood glucose, and food intake was also recorded.

Results: AdipoR1 knockout caused elevated blood glucose and lipids, impaired glucose tolerance and insulin resistance in mice, as well as increased susceptibility to HFD-induced obesity. After 14 days of treatment, WT and AdipoR1^-/- mice showed significant reductions in body weight and blood glucose and improvements in glucose tolerance.

Conclusion: The present study demonstrated that AdipoR1 plays a critical role in metabolic regulation and that the improvement of weight and metabolic function by celastrol is independent of the AdipoR1-mediated signalling pathway.