Several recent studies suggest that celastrol may induce rapid weight loss through several mechanisms as follows: (1) To enhance leptin activity and reduce food intake in obese mice (Greenhill, 2015; Liu et al., 2015); (2) To improve insulin sensitivity via inhibiting NF-κB pathway and control the progression of obesity via enhancing antioxidant capacity and lipid metabolism (Kim et al., 2013; Wang et al., 2014); (3) To activate HSF1–PGC1α transcriptional axis and elicit beneficial metabolic changes against obesity (Ma et al., 2015). The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.