Ursodeoxycholyl lysophosphatidylethanolamide inhibits lipoapoptosis by shifting fatty acid pools toward monosaturated and polyunsaturated fatty acids in mouse hepatocytes

• Verfasst von: Chamulitrat, Walee [VerfasserIn]
• Verfasst von: Liebisch, Gerhard [VerfasserIn]
• Verfasst von: Xu, Weihong [VerfasserIn]
• Verfasst von: Gan-Schreier, Hongying [VerfasserIn]
• Verfasst von: Pathil, Anita [VerfasserIn]
• Verfasst von: Schmitz, Gerd [VerfasserIn]
• Verfasst von: Stremmel, Wolfgang [VerfasserIn]
• Titel: Ursodeoxycholyl lysophosphatidylethanolamide inhibits lipoapoptosis by shifting fatty acid pools toward monosaturated and polyunsaturated fatty acids in mouse hepatocytes
• Verf.angabe: Walee Chamulitrat, Gerhard Liebisch, Weihong Xu, Hongying Gan-Schreier, Anita Pathil, Gerd Schmitz, and Wolfgang Stremmel
• E-Jahr: 2013
• Jahr: August 23, 2013
• Umfang: 14 S.
• Teil: volume:84
• Teil: year:2013
• Teil: number:5
• Teil: pages:696-709
• Teil: extent:14
• Fussnoten: Gesehen am 24.03.2021
• Titel Quelle: Enthalten in: Molecular pharmacology
• Ort Quelle: Bethesda, Md. : ASPET, 1965
• Jahr Quelle: 2013
• Band/Heft Quelle: 84(2013), 5, Seite 696-709
• ISSN Quelle: 1521-0111
• DOI: doi:10.1124/mol.113.088039
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1752356969

Abstract

Ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE) is a hepatoprotectant in inhibiting apoptosis, inflammation, and hyperlipidemia in mouse models of nonalcoholic steatohepatitis (NASH). We studied the ability of UDCA-LPE to inhibit palmitate (Pal)-induced apoptosis in primary hepatocytes and delineate cytoprotective mechanisms. We showed that lipoprotection by UDCA-LPE was mediated by cAMP and was associated with increases in triglycerides (TGs) and phospholipids (PLs). An inhibitor of cAMP-effector protein kinase A partially reversed the protective effects of UDCA-LPE. Lipidomic analyses of fatty acids and PL composition revealed a shift of lipid metabolism from saturated Pal to monounsaturated and polyunsaturated fatty acids, mainly, oleate, docosapentaenoate, and docosahexaenoate. The latter two ω-3 fatty acids were particularly found in phosphatidylcholine and phosphatidylserine pools. The catalysis of Pal by stearoyl-CoA desaturase-1 (SCD-1) is a known mechanism for the channeling of Pal away from apoptosis. SCD-1 protein was upregulated during UDCA-LPE lipoprotection. SCD-1 knockdown of Pal-treated cells showed further increased apoptosis, and the extent of UDCA-LPE protection was reduced. Thus, the major mechanism of UDCA-LPE lipoprotection involved a metabolic shift from toxic saturated toward cytoprotective unsaturated fatty acids in part via SCD-1. UDCA-LPE may thus be a therapeutic agent for treatment of NASH by altering distinct pools of fatty acids for storage into TGs and PLs, and the latter may protect lipotoxicity at the membrane levels.