科研之友
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摘要
Background: Reduced body weight and fat mass, especially subcutaneous white adipose tissue, were observed in liver X receptor beta knockout (LXR beta(-/-)) compared with Wild Type (WT) mice. The similar results were also observed in liver X receptor alpha and beta double knockout (LXR alpha beta(-/-)) mice. However, liver X receptor a knockout (LXR alpha(-/-)) mice had normal body weight and fat mass. Conversely, brown adipose tissue, an energy expenditure-related thermogenic tissue, was reduced only in LXR alpha(-/-) mice compared with WT mice. Furthermore, specific knockout of LXR alpha in mouse adipose tissue gained more weight and fat mass on a high-fat diet compared with WT controls. Objective: This study was aimed to explore the role of LXRa activator on its anti-obesity effect. Materials and Methods: The ATI-111, a novel synthetic LXR alpha-selective agonist,was orally administrated to male ob/ob mice once a day for 6 weeks. Animal body weight, dietary intake and blood glucose were measured during the treatment period. Measured values were presented as Mean +/- Standard Error of the Mean (SEM). Differences between means were analyzed for statistical significance (p<0.05) by using unpaired student t-test. Results: A significant weight loss was observed in ATI-111-treated mice compared with vehicle-treated mice after 4 weeks treatment. In the meanwhile, blood glucose levels were remarkably declined in ATI-111-treated mice compared with vehicle-treated mice after 6 weeks treatment. The average daily dietary intake by each mouse, measured every 2 weeks, was tremendously lower in ATI-111-treated mice compared with vehicle-treated mice after 6 weeks treatment. Conclusion:This study indicates that the activation of LXR alpha by ATI-111 may regulate mouse appetite by inhibiting hunger via a leptin-independent mechanism. It also suggests the potential pharmaceutical development to target LXR alpha for the treatment of obesity and type 2 diabetes.
- 出版日期2017
- 单位北京积水潭医院
