Fatty acid amide signaling molecules

Abstract

Key studies leading to the discovery and definition of the role of endogenous fatty acid amide signaling molecules are summarized.

Modulation of Glucagon-like Peptide-1 (GLP-1) Potency by Endocannabinoid-like Lipids Represents a Novel Mode of Regulating GLP-1 Receptor Signaling

“…We probed the potential conformation of GLP-1(7-36) amide based on its susceptibility to trypsin digestion. The two trypsin cleavage products of GLP-1 amide are an inactive GLP-1 (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) and a partially active GLP-1(7-34) (Fig. 8A) (32).…”

“…Here, we report that the specific endogenous endocannabinoid-like lipids oleoylethanolamide (OEA) and 2-oleoylglycerol (2-OG) can bind to GLP-1 peptide and are accompanied by an enhancement of cAMP production. Physiological levels of these lipids are subject to temporal and spatial regulation (17)(18)(19), and alone, they cannot activate GLP-1R signaling. Here, we show that the potency of GLP-1 is modulated by specific lipids, and this may represent a novel mode of spatiotemporal regulation of GLP-1R signaling.…”

Synthesis and Evaluation of Fatty Acid Amides on the <i>N</i>-Oleoylethanolamide-Like Activation of Peroxisome Proliferator Activated Receptor α

“…PPAR-α is a nuclear receptor and a key regulator of lipid metabolism and energy balance in mammals. Thus, PPAR-α agonists such as the ethanolamides of fatty acids [1][2][3][4][5] may have potential as antiobesity or antihyperlipidemic drugs.…”

Synthesis of Linoleoyl Ethanolamide

“…However, linoleoyl ethanolamide has been found to only weakly bind G-protein-coupled cannabinoid receptors of type-1 CB 1 and CB 2 receptors 11 , and is 4-fold less potent than anandamide at causing catalepsy in mice and it does not prolong sleep time 8 . In addition, linoleoyl ethanolamide competitively inhibits the hydrolysis of anandamide 12 and may be involved in the regulation of food intake by selective prolongation of feeding latency and post-meal interval 8 .…”

“…In addition, linoleoyl ethanolamide competitively inhibits the hydrolysis of anandamide 12 and may be involved in the regulation of food intake by selective prolongation of feeding latency and post-meal interval 8 .…”