IDENTIFICATION AND QUANTIFICATION OF STEAROYLISOPROPYLAMIDE, A NEW ENDOGENOUSLY-OCCURING LIPID IN BRAIN TISSUE

Loris Tonidandel1, Luise Diego2, Berto Fiorenzo2, Maurizio Dalle Carbonare2, Alberta Leon2, Pietro Traldi1

1CNR-ISTM, Corso Stati Uniti 4, Padova, Italy
2Research Innovation, Via Svizzera 16, Padova, Italy

Amides of fatty acids, such as simple amides or ethanolamide derivatives of arachidonic, oleic, stearic, or palmitic acid, constitute a large class of endogenous signaling lipids that, because of their structural similarity and modulation of several physiological processes, including inflammation and pain, feeding behaviour, sleep etc., are classified as endocannabinoids or endocannabinoid-like molecules. Indeed, the family of endogenous lipid derivatives related to the endocannabinoids has, in recent years, enormously grown and today consists of at least 4 different classes: N-acyl-ethanolamides, acylamides, acyl-dopamines, acyl amino-acids. However, while the pharmacological effects of some of these lipids (i.e. anandamide) are reportedly mediated, at least in part, by their interaction with the cannabinoid receptors CB1 or CB2, others do not bind with appreciable affinity to either the  CB1 or CB2 receptors.
We here report identification by GC/MS of a new endogenously-occurring lipid molecule in normal adult rodent tissues and cells, namely an unusual stearate derivative structurally related to endocannabinoid-like molecules. In addition, our results show that this molecule, stearoylisopropylamide (SIPA) like palmitoylethanolamide (PEA), accumulates in rodent brain tissue in hypoxic conditions as well as in cultured cells following induction of mitochondrial-uncoupling. Also, when exogenously administered, SIPA, like PEA, displays anti-inflammatory activity. This finding not only further supports the existence of a wide number of newly- recognized lipid mediators capable of contributing to the regulation of cell functions and homeostasis, but also raises, given the unusual nature of the aminic chain, important questions with regard to the metabolic pathways involved in the production/degradation of SIPA in animal tissues.