Using caenorhabditis elegans as a model for obesity pharmacology development
Copyright © 2015 Wolters Kluwer Health, Inc. 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 mg/mL) increased the IFD (12.1 6 0.1%, P < 0.02), which was blocked by betahistine (763 mg/mL, 39.3 6 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.
Publication Source (Journal or Book title)
American Journal of Therapeutics
Zheng, J., Vasselli, J., King, J., King, M., We, W., Fitzpatrick, Z., Johnson, W., Finley, J., Martin, R., Keenan, M., Enright, F., & Greenway, F. (2016). Using caenorhabditis elegans as a model for obesity pharmacology development. American Journal of Therapeutics, 23 (6), e1363-e1370. https://doi.org/10.1097/MJT.0000000000000061