Methylnaltrexone reduced body weight gain in ob/ob mice

Chun-Su Yuan, MD, PhD; Chong-Zhi Wang, PhD; Anoja Attele, MD; Liu Zhang, PhD

doi:10.5055/jom.2009.0023

Authors

Chun-Su Yuan, MD, PhD
Chong-Zhi Wang, PhD
Anoja Attele, MD
Liu Zhang, PhD

DOI:

https://doi.org/10.5055/jom.2009.0023

Keywords:

opioid, naloxone, methylnaltrexone, body weight, food intake, body temperature, energy expenditure, ob/ob mice

Abstract

Objective: Opioids may function to regulate food intake and body weight, an activity that could be predominantly centrally mediated. In this study, the authors evaluated the effects of a peripherally acting opioid receptor antagonist, methylnaltrexone, on weight changes in adult obese ob/ob mice.
Results: After a 12-day treatment with naloxone 0.3 mg/kg, weight was reduced from 63.7 ± 1.1 g in the control group to 59.2 ± 0.9 g in the naloxone group (p < 0.05). After a 12-day treatment with methylnaltrexone 3.0 mg/kg, weight increase completely ceased. The body weight was 63.9 ± 1.0 g in the control group when compared with 55.9 ± 1.2 g in the drug group (p < 0.01). The effect of methylnaltrexone (1.0 mg to 3.0 mg/kg) on weight changes was dose-dependent (p < 0.01). Methylnaltrexone significantly reduced daily food intake (p < 0.05), but did not affect body temperature and energy expenditure. Using HPLC analysis, no detectable naltrexone levels were found in association with methylnaltrexone administration. Whether the observed methylnaltrexone effects are primarily related to the antagonism of endorphinergic system remains to be investigated.
Conclusions: Our results suggest that the peripheral opioid mechanism contributes to modulating food ingestion and methylnaltrexone may have clinical importance in obesity management.

Author Biographies

Chun-Su Yuan, MD, PhD

Department of Anesthesia and Critical Care, Pritzker School of Medicine, University of Chicago, Chicago, Illinois; Committee on Clinical Pharmacology and Pharmacogenomics, Pritzker School of Medicine, University of Chicago, Chicago, Illinois.

Chong-Zhi Wang, PhD

Department of Anesthesia and Critical Care, Pritzker School of Medicine, University of Chicago, Chicago, Illinois.

Anoja Attele, MD

Department of Anesthesia and Critical Care, Pritzker School of Medicine, University of Chicago, Chicago, Illinois.

Liu Zhang, PhD

Department of Anesthesia and Critical Care, Pritzker School of Medicine, University of Chicago, Chicago, Illinois.

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