RT Journal Article
T1 Plasma Concentrations of Lysophosphatidic Acid and Autotaxin in Abstinent Patients with Alcohol Use Disorder and Comorbid Liver Disease.
A1 Flores-Lopez, Maria
A1 Garcia-Marchena, Nuria
A1 Pavon, Francisco Javier
A1 Lara, Estrella
A1 Porras-Perales, Oscar
A1 Araos, Pedro
A1 Requena-Ocaña, Nerea
A1 Torres-Galvan, Sandra
A1 Mañas-Padilla, M Carmen
A1 Rubio, Gabriel
A1 Suarez, Juan
A1 Santin, Luis J
A1 Rodriguez-de-Fonseca, Fernando
A1 Castilla-Ortega, Estela
A1 Garcia-Fernandez, Maria I
A1 Serrano, Antonia
K1 Alcohol use disorder
K1 Autotaxin
K1 Comorbidity
K1 Liver disease
K1 Lysophosphatidic acid
AB Lysophosphatidic acid (LPA) is an endogenous lysophospholipid and a bioactive lipid that is synthesized by the enzyme autotaxin (ATX). The ATX-LPA axis has been associated with cognitive dysfunction and inflammatory diseases, mainly in a range of nonalcoholic liver diseases. Recently, preclinical and clinical evidence has suggested a role of LPA signaling in alcohol use disorder (AUD) and AUD-related cognitive function. However, the ATX-LPA axis has not been sufficiently investigated in alcoholic liver diseases. An exploratory study was conducted in 136 participants, 66 abstinent patients with AUD seeking treatment for alcohol (alcohol group), and 70 healthy control subjects (control group). The alcohol group was divided according to the presence of comorbid liver diseases (i.e., fatty liver/steatosis, alcoholic steatohepatitis, or cirrhosis). All participants were clinically evaluated, and plasma concentrations of total LPA and ATX were measured using enzyme-linked immunosorbent assays. Data were primarily analyzed using analysis of covariance (ANCOVA) while controlling for age, body mass index, and sex. Logistic regression models were created to assess the association of the ATX-LPA axis and AUD or liver disease. LPA and ATX were log10-transformed to fit the assumptions of parametric testing.The main results were as follows: total LPA and ATX concentrations were dysregulated in the alcohol group, and patients with AUD had significantly lower LPA (F(1,131) = 10.677, p = 0.001) and higher ATX (F(1,131) = 8.327, p = 0.005) concentrations than control subjects; patients with AUD and liver disease had significantly higher ATX concentrations (post hoc test, p < 0.05) than patients with AUD but not liver disease; significant correlations between AUD-related variables and concentrations of LPA and ATX were only found in the non-liver disease subgroup (the duration of alcohol abstinence with LPA and ATX (r = +0.33,p < 0.05); and the severity of AUD with ATX (rho = −0.33, p < 0.05)); and a logistic regression model  with LPA, ATX, and AUD-related variables showed an excellent discriminative power (area under the curve (AUC) = 0.915, p < 0.001) for distinguishing patients with AUD and comorbid liver disease.In conclusion, our data show that the ATX–LPA axis is dysregulated in AUD and suggest this lipid signaling, in combination with relevant AUD-related variables, as a reliable biomarker of alcoholic liver diseases.
PB MDPI
SN 2227-9059
YR 2021
FD 2021-09-13
LK http://hdl.handle.net/10668/18553
UL http://hdl.handle.net/10668/18553
LA en
NO Flores-López M, García-Marchena N, Pavon FJ, Lara E, Porras-Perales O, Araos P, et al. Plasma Concentrations of Lysophosphatidic Acid and Autotaxin in Abstinent Patients with Alcohol Use Disorder and Comorbid Liver Disease. Biomedicines. 2021 Sep 13;9(9):1207
NO The present study has been supported by the following programs and research projects: Subprograma Redes Temáticas RETICS (Red de Trastornos Adictivos RD16/0017/0001) funded by Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad and the European Regional Development Funds/European Social Fund (ERDF/ESF); Proyectos de Investigación en Salud (PI17/02026, PI19/00886, PI19/01577 and PI20/01399) funded by ISCIII and ERDF/ESF; Proyectos de Investigación en Drogodependencias (PND2017/043, PND2018/033, PNSD2018/044 and PND2019/040) funded by Delegación del Gobierno para el Plan Nacional sobre Drogas, Ministerio de Sanidad and ERDF/ESF; Proyectos de Investigación en Salud (PI-194-2014 and PI-0140-2018) funded by Consejería de Salud y Familias, Junta de Andalucía and ERDF/ES; Proyectos I + D + I en el marco del Programa Operativo FEDER Andalucía 2014–2020 (UMA18-FEDERJA-004 and UMA18-FEDERJA-059) funded by Consejería de Economía, Conocimiento, Empresas y Universidad, Junta de Andalucía and ERDF/ES; and Plan Propio de Investigación y Transferencia de la Universidad de Málaga (Ayudas para proyectos puente B4 to E.C.O.). NGM holds a “Sara Borrell” research contract (CD19/00019) funded by ISCIII and ERDF/ESF. FJP and AS hold a “Miguel Servet II” research contract (CPII19/00022 and CPII19/00031, respectively) funded by ISCIII and ERDF/ESF. MFL holds a "PFIS" research contract (FI18/00249) funded by ISCIII and ERDF/ESF.
DS RISalud
RD Apr 15, 2025