Plasma Concentrations of Lysophosphatidic Acid and Autotaxin in Abstinent Patients with Alcohol Use Disorder and Comorbid Liver Disease
María Flores-López,
Nuria García-Marchena,
Francisco Javier Pavon,
Estrella Lara,
Oscar Porras-Perales,
Pedro Araos,
Nerea Requena-Ocaña,
Sandra Torres-Galván,
M. Carmen Mañas-Padilla,
Gabriel Rubio,
Juan Suárez,
Luis J. Santín,
Fernando Rodríguez de Fonseca,
Estela Castilla-Ortega,
María I. García-Fernández,
Antonia Serrano
Affiliations
María Flores-López
Instituto de Investigación Biomédica de Málaga—IBIMA, 29071 Málaga, Spain
Nuria García-Marchena
Instituto de Investigación Biomédica de Málaga—IBIMA, 29071 Málaga, Spain
Francisco Javier Pavon
Instituto de Investigación Biomédica de Málaga—IBIMA, 29071 Málaga, Spain
Estrella Lara
Departamento de Fisiología Humana, Histología Humana, Anatomía Patológica Y Educación Física y Deportiva, Facultad de Medicina, Universidad de Málaga, 29071 Málaga, Spain
Oscar Porras-Perales
Instituto de Investigación Biomédica de Málaga—IBIMA, 29071 Málaga, Spain
Pedro Araos
Instituto de Investigación Biomédica de Málaga—IBIMA, 29071 Málaga, Spain
Nerea Requena-Ocaña
Instituto de Investigación Biomédica de Málaga—IBIMA, 29071 Málaga, Spain
Sandra Torres-Galván
Instituto de Investigación Biomédica de Málaga—IBIMA, 29071 Málaga, Spain
M. Carmen Mañas-Padilla
Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, 29071 Málaga, Spain
Gabriel Rubio
Servicio de Psiquiatría, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain
Juan Suárez
Instituto de Investigación Biomédica de Málaga—IBIMA, 29071 Málaga, Spain
Luis J. Santín
Instituto de Investigación Biomédica de Málaga—IBIMA, 29071 Málaga, Spain
Fernando Rodríguez de Fonseca
Instituto de Investigación Biomédica de Málaga—IBIMA, 29071 Málaga, Spain
Estela Castilla-Ortega
Instituto de Investigación Biomédica de Málaga—IBIMA, 29071 Málaga, Spain
María I. García-Fernández
Departamento de Fisiología Humana, Histología Humana, Anatomía Patológica Y Educación Física y Deportiva, Facultad de Medicina, Universidad de Málaga, 29071 Málaga, Spain
Antonia Serrano
Instituto de Investigación Biomédica de Málaga—IBIMA, 29071 Málaga, Spain
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 p p 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.
