Autotaxin-LPA-LPP3 Axis in Energy Metabolism and Metabolic Disease

Abstract

Besides serving as a structural membrane component and intermediate of the glycerolipid metabolism, lysophosphatidic acid (LPA) has a prominent role as a signaling molecule through its binding to LPA receptors at the cell surface. Extracellular LPA is primarily produced from lysophosphatidylcholine (LPC) through the activity of secreted lysophospholipase D, autotaxin (ATX). The degradation of extracellular LPA to monoacylglycerol is mediated by lipid phosphate phosphatases (LPPs) at the cell membrane. This review summarizes and interprets current literature on the role of the ATX-LPA-LPP3 axis in the regulation of energy homeostasis, insulin function, and adiposity at baseline and under conditions of obesity. We also discuss how the ATX-LPA-LPP3 axis influences obesity-related metabolic complications, including insulin resistance, fatty liver disease, and cardiomyopathy.

Distinct infant feeding type-specific plasma metabolites at age 3 months associate with body composition at 2 years

“…We found most differences in plasma metabolite levels at age 3 months, between low and high tertile body fat mass infants at age 2 years to be apparent in EBF-infants, while only a few associations were seen for EFF-infants. Lyso-phospholipids are phospholipids with only one fatty acid attached to the glycerol backbone and are mostly the result of the hydrolysis of phospholipids by lipases [26] and through the autotaxin-LysoPA-lipid phosphate phosphatase 3 axis [27]. Several of the identified metabolites (dimethylarginine, LysoPA, LysoPS, LysoPE and LysoPG) are known to be associated with proinflammatory pathways in preadipocytes [28,29] and with inflammatory processes [30e32], mainly via interaction with Tolllike receptor dimers [33] and peroxisome proliferator-activated receptor gamma (PPAR-g) [34], and/or the development of cardiovascular disease via G protein-coupled receptors (GPCRs) [35].…”

Lowering of lysophosphatidylcholines in ovariectomized rats by Curcuma comosa

“…In mice, hyperlipidemia is implicated in contributing to circulating LPA [ 38 ]. Several reports have shown the role of adipocyte ATX-LPA axis in obesity and pathogenesis of related diseases [ 39 – 41 ]. Adipocyte-derived ATX constitutes almost half of plasma LPA [ 42 ], and the expression and release of ATX from adipocytes activate preadipocyte proliferation [ 43 ].…”

Effects of a 12-week whole-grain or refined wheat intervention on plasma acylcarnitines, bile acids and signaling lipids, and association with liver fat: A post-hoc metabolomics study of a randomized controlled trial

“…Although actual LPA levels were not measured in the majority of these cross-sectional studies, it can be expected that LPA levels are similarly elevated in these conditions, since serum autotaxin levels are strongly positively correlated to plasma LPA levels ( 37 , 41 ). In mice, heterozygous knockout of ATX, resulting in 50% reduced circulating LPA levels, has been reported to mitigate high-fat diet-induced liver fat accumulation and inflammation ( 42 ). In contrast to these findings, we observed an increase in plasma LPA(18:2) and prevention of liver fat accumulation upon WGW consumption, as compared to RW, as well as an inverse correlation between change in plasma LPA(18:2) and change in CRP, with increases in LPA(18:2) thus being accompanied by a reduction in systemic inflammation.…”