Novel N‐Acylethanolamide Derivatives Affect Body Weight and Energy Balance

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...

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Bibliographic Details
Published in:Chemistry & biodiversity 2023-08, Vol.20 (8), p.e202300212-n/a
Main Authors: Avraham, Yosefa, Berry, Elliot M., Merchavia, Shira, Vorobiev, Lia, Najajreh, Yousef, Furman, Svetlana, Zwas, Donna R., Albeck, Amnon
Format: Article
Language:English
Subjects:
Abstract
acylethanolamides
Appetite
Body weight
Body weight loss
Carbonyl compounds
Carbonyls
Catecholamines
Cognitive ability
cognitive function
Energy balance
Fatty-acid amide hydrolase
Field tests
Food
Food consumption
molecular mechanism of action
Motor activity
Neuropeptide Y
Obesity
Open-field behavior
Proopiomelanocortin
Serotonin
survival
Weight control
Weight loss
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Summary: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.
ISSN:1612-1872
1612-1880
DOI:10.1002/cbdv.202300212