Changes in Liver Lipidomic Profile in G2019S- LRRK2 Mouse Model of Parkinson's Disease

Cells. 2023 Mar 4;12(5):806. doi: 10.3390/cells12050806.

Abstract

The identification of Parkinson's disease (PD) biomarkers has become a main goal for the diagnosis of this neurodegenerative disorder. PD has not only been intrinsically related to neurological problems, but also to a series of alterations in peripheral metabolism. The purpose of this study was to identify metabolic changes in the liver in mouse models of PD with the scope of finding new peripheral biomarkers for PD diagnosis. To achieve this goal, we used mass spectrometry technology to determine the complete metabolomic profile of liver and striatal tissue samples from WT mice, 6-hydroxydopamine-treated mice (idiopathic model) and mice affected by the G2019S-LRRK2 mutation in LRRK2/PARK8 gene (genetic model). This analysis revealed that the metabolism of carbohydrates, nucleotides and nucleosides was similarly altered in the liver from the two PD mouse models. However, long-chain fatty acids, phosphatidylcholine and other related lipid metabolites were only altered in hepatocytes from G2019S-LRRK2 mice. In summary, these results reveal specific differences, mainly in lipid metabolism, between idiopathic and genetic PD models in peripheral tissues and open up new possibilities to better understand the etiology of this neurological disorder.

Keywords: LRRK2; Parkinson; lipids; liver; metabolome; neurodegeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Disease Models, Animal
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / genetics
  • Lipidomics
  • Liver / metabolism
  • Metabolomics
  • Mice
  • Parkinson Disease* / metabolism

Substances

  • Biomarkers
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Lrrk2 protein, mouse

Grants and funding

This research was supported by “Instituto de Salud Carlos III”, “Fondo de Investigaciones Sanitarias” (PI15/0034), “CIBERNED-ISCIII” (CB06/05/0041 and 2015/03), and partially supported by “European Regional Development Fund (ERDF)” from the European Union. J.M.B.-S.P. is funded by “Ramon y Cajal Program” (RYC-2018-025099-I) and supported by Spain’s Ministerio de Ciencia e Innovación (PID2019-108827RA-I00). Y.C.N. and L.M.G. are funded by Community of Madrid (CT5/21/PEJ-2020-TL/BMD-17685 and CT36/22-41-UCM-INV respectively). S.M.S.Y.-D. was supported by CIBERNED-ISCIII. P.M.-C. is funded by the MINECO Spanish Ministry (FPI grant, PRE2020-092668). M.N.-S. was funded by “Ramon y Cajal Program” (RYC-2016-20883). E.U.-C. and S.C.-C. were supported by an FPU predoctoral fellowship (FPU16/00684) and FPU19/04435), respectively, from “Ministerio de Educación, Cultura y Deporte”. M.P-B was funded by a University of Extremadura fellowship. E.A-C was supported by a Grant (IB18048) from Junta de Extremadura, Spain. J.M.F. received research support from the “Instituto de Salud Carlos III”; “Fondo de Investigaciones Sanitarias” (PI15/0034) and CIBERNED-ISCIII (CB06/05/0041 and 2015/03). A.P.-C. was supported by MINECO (SAF2014-52940-R and SAF2017-85199-P). J.P.-T. received funding from CIBERNED-ISCIII (CB06/05/1123 and 2015/03). G.K. is supported by the Ligue contre le Cancer (équipe labellisée); Agence National de la Recherche (ANR)—Projets blancs; ANR under the frame of E-Rare-2, the ERANet for Research on Rare Diseases; AMMICa US/CNRS UMS3655; Association pour la recherche sur le cancer (ARC); Association “Le Cancer du Sein, Parlons-en!”; Cancéropôle Ile de-France; Chancelerie des universités de Paris (Legs Poix), Fondation pour la Recherche Médicale (FRM); a donation by Elior; European Research Area Network on Cardiovascular Diseases (ERA-CVD, MINOTAUR); Gustave Roussy Odyssea, the European Union Horizon 2020 Project Oncobiome; Fondation Carrefour; High-end Foreign Expert Program in China (GDW20171100085), Institut National du Cancer (INCa); Inserm (HTE); Institut Universitaire de France; LeDucq Foundation; the LabEx Immuno-Oncology (ANR-18-IDEX-0001); the RHU Torino Lumière; the Seerave Foundation; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); and the SIRIC Cancer Research and Personalized Medicine (CARPEM).