Abstract
A long-acting cocaine hydrolase, known as CocH3-Fc(M3), engineered from human butyrylcholinesterase (BChE) was tested, in this study, for its potential anti-obesity effects. Mice on a high-fat diet gained significantly less body weight when treated weekly with 1 mg/kg CocH3-Fc(M3) compared to control mice, though their food intake was similar. There is no correlation between the average body weight and the average food intake, which is consistent with the previously reported observation in BChE knockout mice. In addition, molecular modeling was carried out to understand how ghrelin binds with CocH3, showing that ghrelin binds with CocH3 in a similar mode as ghrelin binding with wild-type human BChE. The similar binding structures explains why CocH3 and BChE have similar catalytic activity against ghrelin.
| Original language | English |
|---|---|
| Pages (from-to) | 99-103 |
| Number of pages | 5 |
| Journal | Chemico-Biological Interactions |
| Volume | 259 |
| DOIs | |
| State | Published - Nov 25 2016 |
Bibliographical note
Publisher Copyright:© 2016 Elsevier Ireland Ltd
Funding
This work was supported in part by the National Institutes of Health through the NIDA Translational Avant-Garde Award ( UH2 DA041115 ) and R01 grants ( R01 DA035552 , R01 DA032910 , R01 DA013930 , and R01 DA025100 ) and the National Science Foundation through grant CHE-1111761 . The authors also acknowledge the Computer Center at University of Kentucky for supercomputing time on a Dell X-series Cluster with 384 nodes or 4768 processors.
| Funders | Funder number |
|---|---|
| National Science Foundation Arctic Social Science Program | CHE-1111761 |
| National Institutes of Health (NIH) | |
| National Institute on Drug Abuse | R01 DA035552, R01DA013930, UH2 DA041115, R01 DA025100, R01 DA032910 |
Keywords
- Appetite control
- Cocaine hydrolase
- Enzyme
- Hormone
- Obesity
ASJC Scopus subject areas
- Toxicology
