Given the recent demonstration that oleoylethanolamide (OEA), a cannabinoid receptor-inactive N-acylethanolamine, decreases food intake by activating the nuclear receptor PPARalpha (peroxisome proliferator-activated receptor alpha) in the periphery, we here evaluated the effects of both saturated and unsaturated C18 N-acylethanolamides (C18:0; C18:1; C18:2) in mice feeding behavior after overnight starvation. Our results show stearoylethanolamide (SEA, C18:0) exerts, unlike other unsaturated C18 homologs, a marked dose-dependent anorexic effect evident already at 2 h after its intraperitoneal administration. In addition, oral administration of SEA (25 mg/kg) was also effective in reducing food consumption, an effect ascribed to the molecule itself and not to its catabolites. Moreover, although the anorexic response to oral administered SEA was not associated with changes in the levels of various hematochemical parameters (e.g., glucose, cholesterol, triglycerides, leptin) nor in liver mRNA expression of peroxisome proliferator-activated receptors (PPARs) including PPARalpha, the anorexic effect of SEA was interestingly accompanied by a reduction in liver stearoyl-CoA desaturase-1 (SCD-1) mRNA expression. As SCD-1 has been recently proposed as a molecular target for the treatment of obesity, the novel observation provided here that SEA reduces food intake in mice in a structurally selective manner, in turn, correlated with downregulation of liver SCD-1 mRNA expression, has the potential of providing new insights on a class of lipid mediators with suitable properties for the pharmacological treatment of over-eating dysfunctions.
Fatty acid amides (FAAs), such as the N-acylamides, N-acylethanolamides, N-acyldopamines and N-acylamino acids, are now emerging as an important new class of lipid-signalling molecules. This paper provides evidence, based on high-performance liquid chromatography/electrospray ionisation mass spectrometry (HPLC/ESI-MS/MS), gas chromatography/mass spectrometry (GC/MS) and 1H-NMR, of the occurrence in mouse and bovine brain extracts of a compound characterised by a mass spectrum attributable to a FAA not previously described, namely, the isopropyl-amide of stearic acid (SIPA). A highly sensitive GC/MS method was developed for quantification of naturally occurring SIPA and, also, for purposes of comparison, that of palmitoylethanolamide (PEA), a structurally related compound commonly determined in animal tissues. The results obtained show that SIPA levels in mouse brain are 8-10-fold higher than those of PEA. Moreover, SIPA was found in human neuroblastoma cell (SHSY-5Y) extracts, at significantly higher levels following exposure of the cells to the mitochondrial inhibitor rotenone. All this evidence not only shows surprisingly that SIPA may be found naturally in mammalian biological extracts despite the unusual functional group (i.e. isopropylamide) implicated, but also raises many important questions concerning its biological origin.
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