Celastrol Improves Preference for a Fatty Acid, and Taste Bud and Systemic Inflammation in Diet-Induced Obese Mice
2025
Manal Benmouna | Chahid Benammar | Amira Sayed Khan | Fatima Zohra Djeziri | Aziz Hichami | Naim A. Khan
Background: Obesity is associated with the altered gustatory perception of dietary fatty acids. Celastrol, a triterpene, has been demonstrated to exert anti-obesity effects in rodents. We assessed the role of Celastrol in the modulation of the oro-sensory perception of lipids in control and high-fat diet (HFD)-induced obese mice. Methods: Male mice of the C57B/6J strain were fed a HFD for 11 weeks and then were administered or not with Celastrol further for 4 weeks. The body weight was recorded weekly. Before the sacrifice, the animals were subjected to oro-sensory detection of a dietary long-chain fatty acid in a two-bottle choice paradigm. After the sacrifice, the fungiform taste buds were isolated and analyzed for mRNA expression, encoding fat sensors (CD36 and GPR120) and pro-inflammatory cytokines (IL-1&beta:, IL-6 and TNF-&alpha:). Circulating concentrations of IL-6 and TNF-&alpha: were also determined, and liver was used to analyze the mRNA expression of lipogenic genes. Results: Celastrol administration in obese mice decreased body weight and also re-established the loss of oro-sensory perception for a dietary fatty acid, and this phenomenon was, in part, due to the upregulation of mRNA, encoding fat taste receptors (CD36 and GPR120) in tongue taste bud cells. Furthermore, Celastrol decreased inflammation both in taste buds and blood circulation. Conclusions: Our findings suggest that Celastrol decreases body weight gain, ameliorates the gustatory perception of lipids, and downregulates inflammation in obese mice.
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