In summary, different animal experiments confirmed that celastrol had metabolic improvement effect on HFD induced SD rats/mice or aged-obesity mice, but has no effect on gene deficiency mice such as HSF1 deletion mice, IL1R1 null mice, Sirt1 deficient mice, etc. (Ma et al., 2015; Zhang et al., 2017a; Feng et al., 2019b). Here, SIRT1 is linked to obesity due to melanocortin 4 receptor deficiency.