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.
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.
Huang
Linfang
L
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Beijing 1000193, China.
Toyoshima
Megumi
M
Asakawa
Akihiro
A
Inoue
Kayoko
K
Harada
Kouji
K
Kinoshita
Tomomi
T
Chen
Shilin
S
Koizumi
Akio
A
D000818:Animals; D019440:Anti-Obesity Agents; D001067:Appetite Depressants / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D004983:Ethanolamines / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006943:Hyperglycemia / Q000188:drug therapy*; D006963:Hyperphagia / Q000188:drug therapy* / Q000523:psychology; D007004:Hypoglycemic Agents; D007276:Injections, Intraventricular; D007306:Insecticides / Q000008:administration & dosage / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology; D063086:Organothiophosphates / Q000008:administration & dosage / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects
D019440:Anti-Obesity Agents; D001067:Appetite Depressants; D001786:Blood Glucose; D004983:Ethanolamines; D007004:Hypoglycemic Agents; D007306:Insecticides; C022203:N-acylethanolamines; D063086:Organothiophosphates; C019123:O,O,S-trimethyl phosphorothioate