The underlying molecular mechanism of celastrol anti-obesity and increase the leptin sensitivity can be attributed to Sirtuin 1(Sirt1) (Zhang et al., 2017a; Abu Bakar et al., 2020), interleukin-1 receptor 1(IL1R1) (Feng et al., 2019b), protein tyrosine phosphatase (PTP) 1B (PTP1B), and T-cell PTP (TCPTP) (Kyriakou et al., 2018). The gene discussed is LEP; the disease is obesity due to melanocortin 4 receptor deficiency.