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Review
. 2018 Mar 23;10(4):399.
doi: 10.3390/nu10040399.

Lysophosphatidic Acid Signaling in Obesity and Insulin Resistance

Kenneth D'Souza  1 , Geena V Paramel  2 , Petra C Kienesberger  3
Affiliations
Review

Lysophosphatidic Acid Signaling in Obesity and Insulin Resistance

Kenneth D'Souza et al. Nutrients. .

Abstract

Although simple in structure, lysophosphatidic acid (LPA) is a potent bioactive lipid that profoundly influences cellular signaling and function upon binding to G protein-coupled receptors (LPA1-6). The majority of circulating LPA is produced by the secreted enzyme autotaxin (ATX). Alterations in LPA signaling, in conjunction with changes in autotaxin (ATX) expression and activity, have been implicated in metabolic and inflammatory disorders including obesity, insulin resistance, and cardiovascular disease. This review summarizes our current understanding of the sources and metabolism of LPA with focus on the influence of diet on circulating LPA. Furthermore, we explore how the ATX-LPA pathway impacts obesity and obesity-associated disorders, including impaired glucose homeostasis, insulin resistance, and cardiovascular disease.

Keywords: adipocytes; autotaxin; cardiovascular disease; diet; insulin resistance; lysophosphatidic acid; lysophospholipids; obesity.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Metabolism of circulating lysophosphatidic acid (LPA). LPA is either synthesized from phosphatidic acid (PA) through the actions of PLA1/PLA2 or via autotaxin (ATX)-mediated hydrolysis of lysophosphatidylcholine (LPC). Clearance of circulating LPA involves its rapid degradation to monoacylglycerol (MAG) through the actions of LPP1/3 or hepatic uptake of LPA. sPLA2-IIA, group IIA secretory phospholipase A2; mPA-PLA1, membrane-bound PA-selective phospholipase A1; LCAT, lecithin–cholesterol acyltransferase.
Figure 2
Figure 2
Sources of circulating LPA. LPA can be generated from a variety of sources, including lipoproteins, exosomes, activated platelets, and diet.
Figure 3
Figure 3
Potential mechanisms by which ATX-LPA signaling promotes insulin resistance and impaired glucose homeostasis. The ATX-LPA pathway may contribute to obesity-induced insulin resistance by stimulating inflammation and fibrosis and/or suppressing brown adipose tissue (BAT) and mitochondrial function, and PPARγ signaling.
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