| First Author | Yotsumoto T | Year | 2005 |
| Journal | Metabolism | Volume | 54 |
| Issue | 5 | Pages | 573-8 |
| PubMed ID | 15877285 | Mgi Jnum | J:99069 |
| Mgi Id | MGI:3581077 | Doi | 10.1016/j.metabol.2004.11.013 |
| Citation | Yotsumoto T, et al. (2005) A retinoid X receptor antagonist, HX531, improves leptin resistance without increasing plasma leptin level in KK-Ay mice under normal dietary conditions. Metabolism 54(5):573-8 |
| abstractText | 4-(5 H -2,3-(2,5-Dimethyl-2,5-hexano)-5-methyl-8-nitrodibenzo[b,e][1,4]diazepin-1 1-yl)benzoic acid (HX531) is a novel retinoid X receptor antagonist. This study provides evidence that HX531 improves leptin resistance without increasing plasma leptin levels in KK-A y mice, an animal model with high plasma leptin levels and leptin resistance. Under normal dietary conditions, 3 weeks of treatment with HX531 (0.03% and 0.06% food admixture) in KK-A y mice decreased plasma leptin levels in a dose- and time-dependent manner, in addition to decreasing body weight and mesenteric fatty tissue weight. To evaluate the effect of HX531 on leptin resistance, leptin was injected intraperitoneally in the KK-A y mice for 4 days after 1 week of treatment with HX531 (0.06% food admixture). This pretreatment with HX531 resulted in exogenously administered leptin causing a significant decrease in food intake. These results suggested that HX531 decreased plasma leptin levels accompanied by a decrease in fatty tissue content in the KK-A y mice and a simultaneous improvement in leptin resistance. This is the first report that HX531 improves leptin resistance without increasing plasma leptin level in KK-A y mice, under normal dietary conditions. |
