CONICET | Buscador de Institutos y Recursos Humanos

Fatty acids (FAs) are classically associated with structural and metabolic roles, as they can be stored as triglycerides, degraded by oxidation or used in phospholipids´ synthesis, the main components of biological membranes. Recently, it has been shown that these lipids exhibit also regulatory functions in different cell types, and the neuronal tissue should not be strange to this role. For example, the central nervous system is enriched in poly-unsaturated FAs, such as arachidonic acid, which participates in the regulation of membrane fluidity, axonal growth, development and inflammatory response. Alterations in lipid metabolism have been associated with cognitive problems and neurodegenerative diseases, but the molecular mechanism behind these effects remains elusive. These ?lipokines? bind to specific receptors triggering second messenger´s systems and regulating gene expression. Four plasma membrane, G protein coupled receptors that recognize free FAs were identified since 2005, commonly known as FFARs. But their roles in neuronal tissues are yet not fully understood.Our aim is to characterize the mechanisms by which different FAs modulate the differentiation of SH SY5Y cells in vitro, a broadly used model system for studies of neurodegenerative diseases such as Parkinson?s Disease. We evaluated the effect of supplementation with FAs, monitoring Akt expression and phosphorylation levels; Ca+2 release and neurite outgrowth. Our results support a positive role for FAs acting through FFARs in neuronal differentiation, although further studies considering other receptors like PPARs and/or FABPs should also be considered for a wider understanding of FAs´ neuronal effects. Characterization of lipid receptors in the nervous system will provide a framework for a better understanding of their roles in neurophysiology and, potentially, new targets for drug design against aging and neurodegenerative processes.