Figure 5.

The Kdm6a inhibitor GSK‐J4 acts as a leptin sensitizer in mouse models to modulate downstream leptin signaling. A) The db/db mice were injected i.p. daily with vehicle or GSK‐J4 (30 mg kg⁻¹) for 3 weeks. The body weights of obese mice are indicated (n = 10 for each group). The percent decrease (%) in body weight of obese mice was calculated during the treatment. B) The fat weight of perirenal and epididymal adipose tissues was collected after the treatment (n = 10 for each group). C) The average food intake of obese mice was recorded during the second week of treatment (n = 10 for each group). D) The insulin and leptin concentration in the serum of obese mice was examined after 3 weeks of treatment (n = 10 for each group). E) The ob/ob mice were injected i.p. daily with vehicle or GSK‐J4 (30 mg kg⁻¹) in the presence or absence of leptin for 3 weeks. The body weights of obese mice are indicated (n = 10 for each group). The percent decrease (%) in body weight of obese mice was calculated during the treatment. F) The fat weight of perirenal and epididymal adipose tissues was collected after the treatment (n = 10 for each group). G) The average food intake of each group of mice was recorded during the second week of treatment (n = 10 for each group). H) The insulin and leptin concentration of the mice was examined after 3 weeks of treatment (n = 10 for each group). ***p < 0.001; **p < 0.005; *p < 0.05. N.S., not significant. I) ITT assay to detect blood glucose homeostasis in ob/ob mice. ***p < 0.001. J) Real‐time PCR assay to show Cry1 mRNA were significantly reduced by the cotreatment of GSK‐J4 and leptin in the hypothalamus of ob/ob mice. K) Immunoblotting assay indicating the phosphorylation of Ern1 and Stat3 after leptin and GSK‐J4 administration.