Potential association of plasma lysophosphatidic acid (LPA) species with cognitive impairment in abstinent alcohol use disorders outpatients

García-Marchena, Nuria; Pizarro, Nieves; Pavón, Francisco Javier; Martı́nez-Huélamo, Miriam; Flores-López, María; Requena-Ocaña, Nerea; Araos, Pedro; Silva-Peña, Daniel; Suárez, Juan; Santín, Luis J.; Torre, Rafael de la; Fonseca, Fernando Rodrı́guez de; Serrano, Antonia

doi:10.1038/s41598-020-74155-0

Cited by 9 publications

(22 citation statements)

References 60 publications

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“…The present data support a reduction in plasma concentrations of total LPA in patients with a history of AUD, which is in consonance with a recent clinical study from our group [ 5 ]. In contrast, plasma concentrations of ATX were higher in these patients than in controls.…”

Section: Discussionsupporting

confidence: 93%

“…Patients with liver diseases were previously diagnosed by the digestive health service, and we could confirm liver damage through markers of liver function (AST, GGT, and ALT). Since LPA signaling has been reported to be different according to age, weight, and sex [ 5 , 26 ], all statistical analyses were adjusted for these variables as cofactors.…”

Section: Discussionmentioning

confidence: 99%

“…Among potential biomarkers, recent studies have linked the lysophosphatidic acid (LPA, 1- or 2-acyl-sn-glycerol 3-phosphate) species to alcohol-related behaviors and AUD [ 5 , 6 , 7 ]. LPA is an endogenous bioactive lipid with intercellular signaling properties that is detected in various biological samples, such as saliva, activated platelets, semen, or cerebrospinal fluid, though plasma is the major source of this lipid mediator [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, while the plasma levels of LPA are increased in alcohol-withdrawn mice relative to drug-naïve controls, the plasma levels of ATX are decreased [ 7 ]. In addition to these preclinical observations, we have recently examined LPA concentrations in the plasma of abstinent patients diagnosed with AUD [ 5 ]. This exploratory study revealed that plasma concentrations of LPA in patients with AUD are downregulated but correlate with plasma concentrations of relevant different growth factors (i.e., brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1)).…”

Section: Introductionmentioning

confidence: 99%

“…This exploratory study revealed that plasma concentrations of LPA in patients with AUD are downregulated but correlate with plasma concentrations of relevant different growth factors (i.e., brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1)). In addition, the decreased concentrations of LPA were found to be associated with cognitive impairments, which suggests that LPA might be a reliable marker for the detection of executive dysfunction linked to pathological alcohol use [ 5 ]. Although the dysregulation of LPA and cognitive impairment in AUD have been explored considering the high prevalence of psychiatric comorbidity, the potential association with other common non-psychiatric diseases (e.g., alcoholic liver diseases) has not been sufficiently examined.…”

Section: Introductionmentioning

confidence: 99%

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Plasma Concentrations of Lysophosphatidic Acid and Autotaxin in Abstinent Patients with Alcohol Use Disorder and Comorbid Liver Disease

et al. 2021

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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.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Plasma Concentrations of Lysophosphatidic Acid and Autotaxin in Abstinent Patients with Alcohol Use Disorder and Comorbid Liver Disease

et al. 2021

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LPA1 receptors in the lateral habenula regulate negative affective states associated with alcohol withdrawal

Ren

Hou

et al. 2023

Neuropsychopharmacol.

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Plasma concentrations of lysophosphatidic acid and the expression of its receptors in peripheral blood mononuclear cells are altered in patients with cocaine use disorders

et al. 2023

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We have recently reported alterations in the plasma concentrations of lysophosphatidic acid (LPA) in patients with substance use disorders. In order to further explore the potential role of the LPA signaling system as biomarker in cocaine use disorders (CUD) we conducted a cross-sectional study with 105 patients diagnosed with CUD and 92 healthy controls. Participants were clinically evaluated and blood samples were collected to determine plasma concentrations of total LPA and LPA species (16:0-, 18:0-, 18:1-, 18:2-, and 20:4-LPA), and the gene expression of LPA1 and LPA2 receptors in peripheral blood mononuclear cells. We found that patients with CUD had significantly lower plasma concentration of the majority of LPA species, while the mRNA expression of LPA1 receptor was found to be higher than controls. Moreover, we found a positive association between plasma concentration of 20:4-LPA and relevant CUD-related variables: age of onset cocaine use and length of cocaine abstinence. The statistical analysis revealed sex differences in concentrations of total LPA and LPA species, and women showed higher LPA concentrations than men. Furthermore, studies in rats of both sexes showed that plasma concentrations of total LPA were also altered after acute and chronic cocaine administration, revealing a sexual dimorphism in these effects. This study found alterations on the LPA signaling system in both, patients with CUD and rats treated with cocaine. Our results demonstrate that LPA signaling is impacted by CUD and sex, which must be taken into consideration in future studies evaluating LPA as a reliable biomarker for CUD.

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Potential association of plasma lysophosphatidic acid (LPA) species with cognitive impairment in abstinent alcohol use disorders outpatients

Cited by 9 publications

References 60 publications

Plasma Concentrations of Lysophosphatidic Acid and Autotaxin in Abstinent Patients with Alcohol Use Disorder and Comorbid Liver Disease

Plasma Concentrations of Lysophosphatidic Acid and Autotaxin in Abstinent Patients with Alcohol Use Disorder and Comorbid Liver Disease

LPA1 receptors in the lateral habenula regulate negative affective states associated with alcohol withdrawal

Plasma concentrations of lysophosphatidic acid and the expression of its receptors in peripheral blood mononuclear cells are altered in patients with cocaine use disorders

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