Oleoylethanolamide inhibits food intake in free-feeding rats after oral administration

Oveisi, Fariba; Gaetani, Silvana; Eng, Kevin Tai-Pang; Piomelli, Daniele

doi:10.1016/j.phrs.2003.12.006

Cited by 91 publications

(42 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The products were washed 4 times with water (20 ml), dehydrated over sodium sulfate, filtered, and dried under N 2 . The final products were characterized by thin-layer chromatography (TLC) [9] and LC-mass spectrometry (LC-MS), as described below. Purity of the resulting octadecenoylethanolamides was >97%.…”

Section: Methodsmentioning

confidence: 99%

Feeding-induced oleoylethanolamide mobilization is disrupted in the gut of diet-induced obese rodents

Igarashi

DiPatrizio

Narayanaswami

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

View full text Add to dashboard Cite

The gastrointestinal tract plays a critical role in the regulation of energy homeostasis by initiating neural and hormonal responses to the ingestion of nutrients. In addition to peptide hormones, such as cholecystokinin (CKK) and peptide YY (PYY), the lipid-derived mediator oleoylethanolamide (OEA) has been implicated in the control of satiety. Previous studies in humans and rodent models have shown that obesity is associated with changes in CCK, PYY and other gut-derived peptide hormones, which may contribute to decreased satiety and increased energy intake. In the present study, we show that small-intestinal OEA production is disrupted in the gut of diet-induced obese (DIO) rats and mice. In lean rodents, feeding or duodenal infusion of Intralipid® or pure oleic acid stimulate jejunal OEA mobilization. This response is strikingly absent in DIO rats and mice. Confirming previous reports, we found that feeding rats or mice a high-fat diet for 7 days is sufficient to suppress jejunal OEA mobilization. Surprisingly, a similar effect is elicited by feeding rats and mice a high-sucrose low-fat diet for 7 days. Collectively, our findings suggest that high fat-induced obesity is accompanied by alterations in the post-digestive machinery responsible for OEA biosynthesis, which may contribute to reduced satiety and hyperphagia.

show abstract

Section: Methodsmentioning

confidence: 99%

Feeding-induced oleoylethanolamide mobilization is disrupted in the gut of diet-induced obese rodents

Igarashi

DiPatrizio

Narayanaswami

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

View full text Add to dashboard Cite

show abstract

“…Thus, dietary fat is necessary and sufficient to trigger the production of OEA by small intestinal enterocytes. Both peripheral (5-20 mg/kg, IP) and oral (50-200 mg/kg) administration of OEA decreases in a dose-dependent manner food intake in rodents (Gaetani et al, 2003; Oveisi et al, 2004). Moreover, sub-chronic administration of OEA (5 mg/kg once/day for 2 wk, IP) reduces food intake, lowers body weight and decreases serum cholesterol and triglyceride levels in obese Zucker rats, compared to vehicle-treated control (Fu et al, 2005).…”

Section: Homeostatic Regulation Of Energy Balancementioning

confidence: 99%

“…OEA elicits satiety primarily by prolonging the post-meal interval and reducing meal frequency (Gaetani et al, 2003; Oveisi et al, 2004). OEA-induced anorexic response involves i) local activation of the peroxisome proliferator-activated receptor-α, which is implicated in regulating absorption, storage and utilization of dietary fat; ii) stimulation of afferent vagus nerve fibers; and iii) recruitment of appetite-controlling paraventricular nucleus and NTS circuits (Rodriguez de Fonseca et al, 2001; Fu et al, 2003; Evans et al, 2004; Bookout et al, 2006; Lefebvre et al, 2006; Gaetani et al, 2010; Azari et al, 2014; Provensi et al, 2014).…”

Section: Homeostatic Regulation Of Energy Balancementioning

confidence: 99%

Obesity: Current and potential pharmacotherapeutics and targets

Narayanaswami

Dwoskin

2017

Pharmacology & Therapeutics

156

121

View full text Add to dashboard Cite

Obesity is a global epidemic that contributes to a number of health complications including cardiovascular disease, type 2 diabetes, cancer and neuropsychiatric disorders. Pharmacotherapeutic strategies to treat obesity are urgently needed. Research over the past two decades has increased substantially our knowledge of central and peripheral mechanisms underlying homeostatic energy balance. Homeostatic mechanisms involve multiple components including neuronal circuits, some originating in hypothalamus and brain stem, as well as peripherally-derived satiety, hunger and adiposity signals that modulate neural activity and regulate eating behavior. Dysregulation of one or more of these homeostatic components results in obesity. Coincident with obesity, reward mechanisms that regulate hedonic aspects of food intake override the homeostatic regulation of eating. In addition to functional interactions between homeostatic and reward systems in the regulation of food intake, homeostatic signals have the ability to alter vulnerability to drug abuse. Regarding the treatment of obesity, pharmacological monotherapies primarily focus on a single protein target. FDA-approved monotherapy options include phentermine (Adipex-P®), orlistat (Xenical®), lorcaserin (Belviq®) and liraglutide (Saxenda®). However, monotherapies have limited efficacy, in part due to the recruitment of alternate and counter-regulatory pathways. Consequently, a multi-target approach may provide greater benefit. Recently, two combination products have been approved by the FDA to treat obesity, including phentermine/topiramate (Qsymia®) and naltrexone/bupropion (Contrave®). The current review provides an overview of homeostatic and reward mechanisms that regulate energy balance, potential therapeutic targets for obesity and current treatment options, including some candidate therapeutics in clinical development. Finally, challenges in anti-obesity drug development are discussed.

show abstract

“…OEA is a well-established anorexiant factor, a lipid-based satiety signal whose increase in the lumen of the small intestine induces a persistent and selective inhibition of food intake without known adverse reactions [42,[48][49][50][51][52]. Anorexiant agents can curb food ingestion via distinct mode of action such as the reduction of meal size ingested.…”

Section: Obesity Culprit Of Health Life In Westernized Societies: Diementioning

confidence: 99%

The Endocannabinoid-Like Derivative Oleoylethanolamide at the Gut–Brain Interface: A “Lipid Way” to Control Energy Intake and Body Weight

Passani¹,

Coccurello²

2016

Cannabinoids in Health and Disease

View full text Add to dashboard Cite

In the last three decades, we witnessed a concomitant major increase in lifespan and a worldwide increasing incidence of chronic diseases such as obesity and type 2 diabetes. Disruption of energy homeostasis and systemic inflammation appear as common traits of these epidemic human diseases. The conventional endocannabinoid (eCB) system encompasses two G-protein-coupled receptors (GPCRs), their endogenous ligands (anandamide and 2-AG), and the enzymes essential for eCB biosynthesis and hydrolytic inactivation. Nonetheless, the family of eCB-like derivatives is growing constantly including other N-acylethanolamines (NAEs) and 2-monoacylglycerols (2-MAGs) that do not bind canonical CB receptors rather other orphan G-protein-coupled receptors or peroxisome proliferator-activated nuclear receptors (PPARs). Here, we focus on the recent knowledge gathered on one such PPAR endocannabinoid ligand, oleoylethanolamide (OEA), from the identification of its synthesis in the small intestine to its anorexiant function with particular emphasis on our discovery of the main brain neurotransmitters system involved in its satiating effects.

show abstract

Oleoylethanolamide inhibits food intake in free-feeding rats after oral administration

Cited by 91 publications

References 7 publications

Feeding-induced oleoylethanolamide mobilization is disrupted in the gut of diet-induced obese rodents

Feeding-induced oleoylethanolamide mobilization is disrupted in the gut of diet-induced obese rodents

Obesity: Current and potential pharmacotherapeutics and targets

The Endocannabinoid-Like Derivative Oleoylethanolamide at the Gut–Brain Interface: A “Lipid Way” to Control Energy Intake and Body Weight

Contact Info

Product

Resources

About