Levels of N-acylethanolamines in O,O,S-trimethylphosphorothioate (OOS-TMP)-treated C57BL/6J mice and potential anti-obesity, anti-diabetic effects of OOS-TMP in hyperphagia and hyperglycemia mouse models.

Abstract

O,O,S-Trimethylphosphorothioate (OOS-TMP) has been shown to induce hypophagia and hypopraxia. Recent studies suggest that OOS-TMP-induced anorexia is partly mediated by its effect on the central nervous system. In this study, we examined the profiles of N-acylethanolamines (NEAs), including five amide-linked compounds, in the gastrointestinal system in C57BL/6J (B6) mice. The present results shown an orexigenic profile of the levels of NEAs with downregulation of the anorectic lipid, N-stearoylethanolamine (SEA), upregulation of the orexigenic lipid, 2-arachidonoyl glycerol (2-AG), at 2 h and upregulation of 2-AG at 24 h albeit with significant anorexia. However, the data indicated that the high level of 2-AG may be responsible for the hypopraxia. We next explored whether OOS-TMP may affect two models of hyperphagia and hyperglycemia, ins2(+/Akita) B6 (Akita) and B6-lepr(db)/lepr(db) mice (db/db). We identified potential anorexigenic effects in B6, Akita and db/db mice. Moreover, OOS-TMP was found to reduce blood glucose in Akita mice but not in db/db mice. Collectively, these findings suggest that N-acylethanolamines are not involved in the hypophagia but rather hypopraxia, and may play multiple physiological roles in this process. OOS-TMP might be a promising candidate for anti-obesity and anti-diabetic drug development.

• Authors: Linfang Huang, Megumi Toyoshima, Akihiro Asakawa, Kayoko Inoue, Kouji Harada, Tomomi Kinoshita, Shilin Chen, Akio Koizumi
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 92 Issue 1 Pg. 1-5 (Mar 2009) ISSN: 0091-3057 [Print] United States
• PMID: 18992273 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Obesity Agents
• Appetite Depressants
• Blood Glucose
• Ethanolamines
• Hypoglycemic Agents
• Insecticides
• N-acylethanolamines
• Organothiophosphates
• O,O,S-trimethyl phosphorothioate

Topics

• Animals
• Anti-Obesity Agents
• Appetite Depressants (pharmacology)
• Blood Glucose (metabolism)
• Eating (drug effects)
• Ethanolamines (metabolism)
• Gas Chromatography-Mass Spectrometry
• Hyperglycemia (drug therapy)
• Hyperphagia (drug therapy, psychology)
• Hypoglycemic Agents
• Injections, Intraventricular
• Insecticides (administration & dosage, pharmacology)
• Intestinal Mucosa (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Obesity (drug therapy, etiology, psychology)
• Organothiophosphates (administration & dosage, pharmacology)
• Weight Gain (drug effects)