Celastrol (100 μg/kg by intraperitoneally injection [i.p], or 10 mg/kg by oral administration [OA]) increased the leptin sensitivity to suppress food intake and reduce body weight in HFD induced C57BL/6J mice and was firstly reported in 2015 by Ozcan’s group (Liu et al., 2015), while the benefits of celastrol on obesity were abrogated in lean mice, leptin receptor-deficient (db/db), or leptin-deficient (ob/ob) mice/rats (Liu et al., 2015; Pfuhlmann et al., 2018; Feng et al., 2019a; Feng et al., 2019b; Saito et al., 2019; Hu et al., 2020). The gene discussed is LEP; the disease is obesity disorder.