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

Arch Physiol Biochem. 2024 Dec;130(6):642-648. doi: 10.1080/13813455.2023.2250929. Epub 2023 Aug 29.

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.

Keywords: AdipoR1; NAFLD; celastrol; obesity.

MeSH terms

  • Adiponectin* / metabolism
  • Animals
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Diet, High-Fat* / adverse effects
  • Eating / drug effects
  • Insulin Resistance
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout*
  • Obesity* / drug therapy
  • Obesity* / metabolism
  • Pentacyclic Triterpenes* / pharmacology
  • Receptors, Adiponectin* / genetics
  • Receptors, Adiponectin* / metabolism
  • Signal Transduction* / drug effects
  • Triterpenes* / pharmacology

Substances

  • celastrol
  • Pentacyclic Triterpenes
  • Triterpenes
  • Adiponectin
  • Receptors, Adiponectin
  • Blood Glucose
  • adiponectin receptor 1, mouse
  • Adipoq protein, mouse