Fiche publication
Date publication
août 2019
Journal
International journal of molecular sciences
Auteurs
Membres identifiés du Cancéropôle Est :
Dr LAGROST Laurent
,
Pr MASSON David
Tous les auteurs :
Jalil A, Bourgeois T, Ménégaut L, Lagrost L, Thomas C, Masson D
Lien Pubmed
Résumé
Liver X receptors (LXRs) play a pivotal role in fatty acid (FA) metabolism. So far, the lipogenic consequences of in vivo LXR activation, as characterized by a major hepatic steatosis, has constituted a limitation to the clinical development of pharmacological LXR agonists. However, recent studies provided a different perspective. Beyond the quantitative accumulation of FA, it appears that LXRs induce qualitative changes in the FA profile and in the distribution of FAs among cellular lipid species. Thus, LXRs activate the production of polyunsaturated fatty acids (PUFAs) and their distribution into phospholipids via the control of FA desaturases, FA elongases, lysophosphatidylcholine acyltransferase (LPCAT3), and phospholipid transfer protein (PLTP). Therefore, LXRs control, in a dynamic manner, the PUFA composition and the physicochemical properties of cell membranes as well as the release of PUFA-derived lipid mediators. Recent studies suggest that modulation of PUFA and phospholipid metabolism by LXRs are involved in the control of lipogenesis and lipoprotein secretion by the liver. In myeloid cells, the interplay between LXR and PUFA metabolism affects the inflammatory response. Revisiting the complex role of LXRs in FA metabolism may open new opportunities for the development of LXR modulators in the field of cardiometabolic diseases.
Mots clés
inflammation, lipogenesis, liver X receptors, phospholipids, polyunsaturated fatty acids
Référence
Int J Mol Sci. 2019 Aug 2;20(15):
