Novel N-Acylethanolamide Derivatives Affect Body Weight and Energy Balance

Yosefa Avraham, Elliot M. Berry, Shira Merchavia, Lia Vorobiev, Yousef Najajreh, Svetlana Furman, Donna R. Zwas, Amnon Albeck

Research output: Contribution to journalArticlepeer-review


Introduction – The obesity pandemic is multifactorial. Nutritional, pharmacologic and surgical interventions are limited in reach and efficacy, raising need for new therapeutics. Aims – Characterization of anorexigenic and cognitive effect and central mechanism of action of novel N-acylethanolamide derivatives. Methods – Sabra mice divided to similar experimental groups, injected IP with: oleyl-L-leucinolamide (1 A), linoleyl-L-leucinolamide (4 A), linoleyl-L-valinolamide (5 A), oleyl-oxycarbonyl-L-valinolamide (1 B), oleyl-oxycarbonyl-D-valinolamide (2 B), oleylamine-carbonyl-L-valinolamide (3 B), oleylamine-carbonyl-D-valinolamide (4 B), and oleyl-L-hydroxyvalineamide (5 B). Control group with vehicle. Body weight and food consumption followed for 39 days. Motor activity and cognitive function by open field test and eight-arm maze. Mice sacrificed and mechanism of action investigated by qPCR. The genes analyzed involved in energy balance and regulation of appetite. Catecholamines and serotonin evaluated. Results – Compounds 1 A, 5 A, 1 B–4 B, caused significant weight loss of 4.2–5.6 % and 5 A, 1 B–4 B, improved cognitive function following 8 i. p. injections of 1 mg/kg during 39 days, by different mechanisms. 5 A, 3 B and 4 B decreased food consumption, whereas 1 A, 5 A and 2 B increased motor activity. 1 A, 4 A, 1 B and 3 B elevated SIRT-1, associated with survival. POMC upregulated by 1 B and 2 B, CART by 1 B, 2 B and 1 A. NPY and CAMKK2 downregulated by 5 A. 4 B enhanced 5-HT levels. 4 A, 5 A, 1 B, 4 B, 5 B decreased FAAH, showing long lasting effect. Conclusions – These new compounds might be developed for the treatment of obesity and for improved cognitive function.

Original languageEnglish
Article numbere202300212
JournalChemistry and Biodiversity
Issue number8
Early online date18 Jul 2023
StatePublished - Aug 2023


  • Abstract
  • acylethanolamides
  • body weight
  • cognitive function
  • molecular mechanism of action
  • survival

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Chemistry(all)
  • Molecular Medicine
  • Molecular Biology
  • Biochemistry


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