title: Novel acylethanolamide derivatives that modulate body weight through enhancement of hypothalamic pro-opiomelanocortin (POMC) and/or decreased neuropeptide Y (NPY).
abstract: Newly synthesized acylethanolamide derivatives oleoyl-L-valinolamide (1), oleoyl-D-valinolamide (2), elaidoyl-L-valinolamide (3), elaidoyl-D-valinolamide (4) stearoyl-L-valinolamide (5), and palmitoyl-L-valinolamide (6) were investigated in mice as antiobesity compounds. Compounds 1, 2, 5, 6 significantly decreased body weight by 6.57% following eight injections of 1 mg/kg i.p. during 39 days, while 3 and 4 showed no such activity. Receptor binding indicated that no compound activated CB1, CB2, PPARα, or TRPV1 receptors. Hypothalamic RT-PCR showed that mRNA expression of the anorexigenic genes POMC and CART was up-regulated by 1, 2, 5 and 1, 2, respectively, while that of the orexigenic genes NPY and CaMKK2 was down-regulated by the respective compounds 1, 5, 6 and 1, 2, 5. Oleoyl-L-valinolamide enhances anorectic pathways and lead to decreased glucose levels, enhanced locomotor activity, and improved cognition. Effects of oleoyl-L-valinolamide on weight were dose-dependent, and it could be given orally. 1, 2, 4, 5 down-regulated FAAH mRNA expression.
authors: Department of Human Nutrition and Metabolism, Braun School of Public Health, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. yosefa@md.huji.ac.il
authors: Yosefa
authors: Y
authors: Avraham
authors: Jehoshua
authors: J
authors: Katzhendler
authors: Lia
authors: L
authors: Vorobeiv
authors: Shira
authors: S
authors: Merchavia
authors: Chana
authors: C
authors: Listman
authors: Eithan
authors: E
authors: Kunkes
authors: Fida'
authors: F
authors: Harfoush
authors: Sawsan
authors: S
authors: Salameh
authors: Aviva F
authors: AF
authors: Ezra
authors: Nikolaos C
authors: NC
authors: Grigoriadis
authors: Elliot M
authors: EM
authors: Berry
authors: Yousef
authors: Y
authors: Najajreh
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects*; D004435:Eating / Q000187:drug effects; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019906:Nuclear Magnetic Resonance, Biomolecular; D009829:Oleic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis*; D014633:Valine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000577:Amides; D019440:Anti-Obesity Agents; D004983:Ethanolamines; D009478:Neuropeptide Y; D009829:Oleic Acids; C581000:oleoylvalinolamide; D011333:Pro-Opiomelanocortin; D014633:Valine