Figure 4. C/EBP homologous protein (CHOP) plays a key role in regulating soluble isoform of leptin receptor (sOb-R) by the endocannabinoid (eCB)/CB₁R system.

Serum (A, n = 11–18) levels of sOb-R were reduced following a 14 weeks consumption of high-fat diet (HFD). JD5037 (3 mg/kg, for 7 days) reversed the reduction in wild-type (WT), but not CHOP KO mice. Basal hepatic levels of sOb-R were lower in CHOP KO mice and did not change following HFD or JD5037 treatment (B, n = 5–8). A similar trend was observed in hepatic mRNA levels (C, n = 9–17) and protein level of Ob-Rb, Ob-Ra, and Ob-Re (D and E, n = 5–6). Whereas DIO-related hyperleptinemia was comparable between WT and CHOP KO mice, JD5037 was more efficacious in reducing it in WT mice (F, n = 8–16). Lean CHOP KO mice failed to increase the hepatic pSTAT3/STAT3 ratio in response to exogenous leptin administration (G and H, n = 5). Western blots are representative. Data represent mean ± SEM of indicated number of replicates in each panel. *p<0.05 relative to standard diet-fed animals from the same strain. #p<0.05 relative to HFD-fed mice from the same strain. ^p<0.05 relative to the same treatment group of WT mice.