Using Caenorhabditis elegans as a Model for Obesity Pharmacology Development

作者：Zheng, Jolene; Vasselli, Joseph R.; King, Jason F.; King, Michael L.; We, Wenqian; Fitzpatrick, Zachary; Johnson, William D.; Finley, John W.; Martin, Roy J.; Keenan, Michael J.; Enright, Frederic M.; Greenway, Frank L.^*

来源：American Journal of Therapeutics, 2016, 23(6): E1363-E1370.

DOI：10.1097/MJT.0000000000000061

• fat
• energy
• obesity

The Caenorhabditis elegans model is a rapid and inexpensive method to address pharmacologic questions. We describe the use of C. elegans to explore 2 pharmacologic questions concerning candidate antiobesity drugs and illustrate its potential usefulness in pharmacologic research: (1) to determine a ratio of betahistine-olanzapine that blocks the olanzapine-induced intestinal fat deposition (IFD) as detected by Nile red staining and (2) to identify the mechanism of action of a pharmaceutical candidate AB-101 that reduces IFD. Olanzapine (53 g/mL) increased the IFD (12.1 +/- 0.1%, P < 0.02), which was blocked by betahistine (763 g/mL, 39.3 +/- 0.01%, P < 0.05) in wild-type C. elegans (N2). AB-101 (1.0%) reduced the IFD in N2 (P < 0.05), increased the pharyngeal pumping rate (P < 0.05), and reversed the elevated IFD induced by protease inhibitors atazanavir and ritonavir (P < 0.05). AB-101 did not affect IFD in a ACS null mutant strain acs-4(ok2872) III/hT2[bli-4(e937) let-?(q782) qIs48](I;III) suggesting an involvement of the lipid oxidation pathway and an upregulation of CPT-1. Our studies suggest that C. elegans may be used as a resource in pharmacologic research. This article is intended to stimulate a greater appreciation of its value in the development of new pharmaceutical interventions.

• 出版日期2016-11
• 单位复旦大学