RT Journal Article
T1 Plasma Concentrations of Lysophosphatidic Acid and Autotaxin in Abstinent Patients with Alcohol Use Disorder and Comorbid Liver Disease
A1 Flores López, María
A1 García Marchena, Nuria
A1 Pavon, Francisco Javier
A1 Lara, Estrella
A1 Porras Perales, Oscar
A1 Araos, Pedro
A1 Requena Ocaña, Nerea
A1 Torres Galván, Sandra
A1 Mañas Padilla, M. Carmen
A1 Rubio, Gabriel
A1 Suárez, Juan
A1 Santín, Luis J.
A1 Rodríguez de Fonseca, Fernando
A1 Castilla Ortega, Estela
A1 García Fernández, María I.
A1 Serrano, Antonia
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 MPDI
SN 2227-9059
YR 2021
FD 2021-12-13
LK https://hdl.handle.net/20.500.14352/4650
UL https://hdl.handle.net/20.500.14352/4650
LA eng
NO Ministerio de Economía y Competitividad (MINECO)/FEDER
NO Instituto de Salud Carlos III (ISCIII)/FEDER
NO Ministerio de Sanidad/FEDER
NO Junta de Andalucía/FEDER
DS Docta Complutense
RD 28 abr 2024