{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:33:16Z","timestamp":1787585596998,"version":"build-2736575974"},"reference-count":85,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T00:00:00Z","timestamp":1630627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["156308"],"award-info":[{"award-number":["156308"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN 2020-04883"],"award-info":[{"award-number":["RGPIN 2020-04883"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004411","name":"Heart and Stroke Foundation of Canada","doi-asserted-by":"publisher","award":["National New Investigator Award"],"award-info":[{"award-number":["National New Investigator Award"]}],"id":[{"id":"10.13039\/100004411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms22179575","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T13:15:56Z","timestamp":1630934156000},"page":"9575","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Autotaxin-LPA-LPP3 Axis in Energy Metabolism and Metabolic Disease"],"prefix":"10.3390","volume":"22","author":[{"given":"Anu","family":"Jose","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Dalhousie University, Dalhousie Medicine New Brunswick, Saint John, NB E2L 4L5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9643-8338","authenticated-orcid":false,"given":"Petra C.","family":"Kienesberger","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Dalhousie University, Dalhousie Medicine New Brunswick, Saint John, NB E2L 4L5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1152\/physiol.00037.2018","article-title":"Impact of Lipotoxicity on Tissue \u201cCross Talk\u201d and Metabolic Regulation","volume":"34","author":"Montgomery","year":"2019","journal-title":"Physiology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s11906-018-0812-z","article-title":"The Global Epidemic of the Metabolic Syndrome","volume":"20","author":"Saklayen","year":"2018","journal-title":"Curr. Hypertens Rep."},{"key":"ref_3","unstructured":"Freeman, A.M., and Pennings, N. (2021). Insulin Resistance. StatPearls, StatPearls Publishing LLC.. StatPearls Publishing Copyright \u00a9 2021."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.diabres.2018.02.023","article-title":"IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045","volume":"138","author":"Cho","year":"2018","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1161\/CIRCRESAHA.120.315913","article-title":"Basic Mechanisms of Diabetic Heart Disease","volume":"126","author":"Ritchie","year":"2020","journal-title":"Circ. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/j.bbalip.2016.02.016","article-title":"Lipid metabolism and signaling in cardiac lipotoxicity","volume":"1861","author":"Nzirorera","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1111\/joim.12728","article-title":"Manifestations and mechanisms of myocardial lipotoxicity in obesity","volume":"284","author":"Sletten","year":"2018","journal-title":"J. Intern. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1210\/er.2008-0007","article-title":"Glycerolipid metabolism and signaling in health and disease","volume":"29","author":"Prentki","year":"2008","journal-title":"Endocr. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"D\u2019Souza, K., Paramel, G.V., and Kienesberger, P.C. (2018). Lysophosphatidic Acid Signaling in Obesity and Insulin Resistance. Nutrients, 10.","DOI":"10.3390\/nu10040399"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1034\/j.1600-0854.2003.00086.x","article-title":"Modulation of membrane curvature by phosphatidic acid and lysophosphatidic acid","volume":"4","author":"Kooijman","year":"2003","journal-title":"Traffic"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"147","DOI":"10.3389\/fcell.2019.00147","article-title":"The Structure and Function of Acylglycerophosphate Acyltransferase 4\/ Lysophosphatidic Acid Acyltransferase Delta (AGPAT4\/LPAAT\u03b4)","volume":"7","author":"Zhukovsky","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5015","DOI":"10.1128\/MCB.02419-05","article-title":"Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development","volume":"26","author":"Ruurs","year":"2006","journal-title":"Mol. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"18162","DOI":"10.1074\/jbc.M301158200","article-title":"Autotaxin is released from adipocytes, catalyzes lysophosphatidic acid synthesis, and activates preadipocyte proliferation. Up-regulated expression with adipocyte differentiation and obesity","volume":"278","author":"Ferry","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Katsifa, A., Kaffe, E., Nikolaidou-Katsaridou, N., Economides, A.N., Newbigging, S., McKerlie, C., and Aidinis, V. (2015). The Bulk of Autotaxin Activity Is Dispensable for Adult Mouse Life. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0143083"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1124\/jpet.110.165845","article-title":"A novel autotaxin inhibitor reduces lysophosphatidic acid levels in plasma and the site of inflammation","volume":"334","author":"Gierse","year":"2010","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.ydbio.2010.01.007","article-title":"ATX expression and LPA signalling are vital for the development of the nervous system","volume":"339","author":"Fotopoulou","year":"2010","journal-title":"Dev. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"25822","DOI":"10.1074\/jbc.M605142200","article-title":"Autotaxin stabilizes blood vessels and is required for embryonic vasculature by producing lysophosphatidic acid","volume":"281","author":"Tanaka","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1194\/jlr.M014985","article-title":"Adipose-specific disruption of autotaxin enhances nutritional fattening and reduces plasma lysophosphatidic acid","volume":"52","author":"Dusaulcy","year":"2011","journal-title":"J. Lipid Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7385","DOI":"10.1074\/jbc.M807820200","article-title":"Autotaxin\/lysopholipase D and lysophosphatidic acid regulate murine hemostasis and thrombosis","volume":"284","author":"Pamuklar","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1042\/bj3400677","article-title":"Lipid phosphate phosphohydrolase-1 degrades exogenous glycerolipid and sphingolipid phosphate esters","volume":"340","author":"Jasinska","year":"1999","journal-title":"Biochem. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1194\/jlr.M053462","article-title":"Lipid phosphate phosphatase-1 expression in cancer cells attenuates tumor growth and metastasis in mice","volume":"55","author":"Tang","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.atherosclerosis.2018.02.025","article-title":"Lipid phosphate phosphatase 3 in vascular pathophysiology","volume":"271","author":"Busnelli","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1042\/BJ20081888","article-title":"Lipid phosphate phosphohydrolase type 1 (LPP1) degrades extracellular lysophosphatidic acid in vivo","volume":"419","author":"Tomsig","year":"2009","journal-title":"Biochem. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/1526-968X(200008)27:4<137::AID-GENE10>3.0.CO;2-4","article-title":"Mice mutant for Ppap2c, a homolog of the germ cell migration regulator wunen, are viable and fertile","volume":"27","author":"Zhang","year":"2000","journal-title":"Genesis"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9297","DOI":"10.1074\/jbc.M511710200","article-title":"Lipid phosphate phosphatase-2 activity regulates S-phase entry of the cell cycle in Rat2 fibroblasts","volume":"281","author":"Morris","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"S225","DOI":"10.1194\/jlr.R800055-JLR200","article-title":"Lipid phosphate phosphatases and signaling","volume":"50","author":"Brindley","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4623","DOI":"10.1242\/dev.00635","article-title":"The lipid phosphatase LPP3 regulates extra-embryonic vasculogenesis and axis patterning","volume":"130","author":"Hernandez","year":"2003","journal-title":"Development"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"44503","DOI":"10.1038\/srep44503","article-title":"Liver-specific deletion of the Plpp3 gene alters plasma lipid composition and worsens atherosclerosis in apoE(\u2212\/\u2212) mice","volume":"7","author":"Busnelli","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Federico, L., Yang, L., Brandon, J., Panchatcharam, M., Ren, H., Mueller, P., Sunkara, M., Escalante-Alcalde, D., Morris, A.J., and Smyth, S.S. (2018). Lipid phosphate phosphatase 3 regulates adipocyte sphingolipid synthesis, but not developmental adipogenesis or diet-induced obesity in mice. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0198063"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.redox.2017.09.015","article-title":"Cardiac-specific inactivation of LPP3 in mice leads to myocardial dysfunction and heart failure","volume":"14","author":"Chandra","year":"2018","journal-title":"Redox Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1194\/jlr.M039685","article-title":"Mechanism of rapid elimination of lysophosphatidic acid and related lipids from the circulation of mice","volume":"54","author":"Salous","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.biochi.2013.04.010","article-title":"Involvement of autotaxin\/lysophosphatidic acid signaling in obesity and impaired glucose homeostasis","volume":"96","author":"Rancoule","year":"2014","journal-title":"Biochimie"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.1194\/jlr.M075655","article-title":"Blocking gp130 signaling suppresses autotaxin expression in adipocytes and improves insulin sensitivity in diet-induced obesity","volume":"58","author":"Sun","year":"2017","journal-title":"J. Lipid Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1007\/s00125-013-2891-3","article-title":"Lysophosphatidic acid impairs glucose homeostasis and inhibits insulin secretion in high-fat diet obese mice","volume":"56","author":"Rancoule","year":"2013","journal-title":"Diabetologia"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1111\/jcmm.14005","article-title":"Autotaxin\/lysophosphatidic acid signaling mediates obesity-related cardiomyopathy in mice and human subjects","volume":"23","author":"Weng","year":"2019","journal-title":"J. Cell Mol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3403","DOI":"10.1194\/jlr.M042051","article-title":"Transgenic 6F tomatoes act on the small intestine to prevent systemic inflammation and dyslipidemia caused by Western diet and intestinally derived lysophosphatidic acid","volume":"54","author":"Navab","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1111\/j.1476-5381.2012.02021.x","article-title":"Lysophosphatidic acid in atherosclerotic diseases","volume":"167","author":"Schober","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1159\/000480470","article-title":"Lysophosphatidic Acid Inhibits Insulin Signaling in Primary Rat Hepatocytes via the LPA3 Receptor Subtype and is Increased in Obesity","volume":"43","author":"Fayyaz","year":"2017","journal-title":"Cell Physiol. Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/s12944-017-0536-0","article-title":"Lysophosphatidic acid plasma concentrations in healthy subjects: Circadian rhythm and associations with demographic, anthropometric and biochemical parameters","volume":"16","author":"Michalczyk","year":"2017","journal-title":"Lipids Health Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1194\/jlr.R046458","article-title":"LPA receptor signaling: Pharmacology, physiology, and pathophysiology","volume":"55","author":"Yung","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"48737","DOI":"10.1074\/jbc.M206812200","article-title":"Serum lysophosphatidic acid is produced through diverse phospholipase pathways","volume":"277","author":"Aoki","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.ab.2007.05.004","article-title":"Suppression of lysophosphatidic acid and lysophosphatidylcholine formation in the plasma in vitro: Proposal of a plasma sample preparation method for laboratory testing of these lipids","volume":"367","author":"Nakamura","year":"2007","journal-title":"Anal. Biochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"100029","DOI":"10.1016\/j.jlr.2021.100029","article-title":"Suppressing postcollection lysophosphatidic acid metabolism improves the precision of plasma LPA quantification","volume":"62","author":"Kano","year":"2021","journal-title":"J. Lipid Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1194\/jlr.D050070","article-title":"Challenges in accurate quantitation of lysophosphatidic acids in human biofluids","volume":"55","author":"Onorato","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Heimerl, S., Fischer, M., Baessler, A., Liebisch, G., Sigruener, A., Wallner, S., and Schmitz, G. (2014). Alterations of plasma lysophosphatidylcholine species in obesity and weight loss. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0111348"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Barber, M.N., Risis, S., Yang, C., Meikle, P.J., Staples, M., Febbraio, M.A., and Bruce, C.R. (2012). Plasma lysophosphatidylcholine levels are reduced in obesity and type 2 diabetes. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041456"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Pik\u00f3, P., P\u00e1l, L., Sz\u0171cs, S., K\u00f3sa, Z., S\u00e1ndor, J., and \u00c1d\u00e1ny, R. (2021). Obesity-Related Changes in Human Plasma Lipidome Determined by the Lipidyzer Platform. Biomolecules, 11.","DOI":"10.3390\/biom11020326"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"102520","DOI":"10.1016\/j.ebiom.2019.10.046","article-title":"Lipidomic profiling identifies signatures of metabolic risk","volume":"51","author":"Yin","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.bbrc.2004.11.120","article-title":"Lysophosphatidylcholine enhances glucose-dependent insulin secretion via an orphan G-protein-coupled receptor","volume":"326","author":"Soga","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.mce.2017.12.002","article-title":"Lysophosphatidylcholine and its phosphorothioate analogues potentiate insulin secretion via GPR40 (FFAR1), GPR55 and GPR119 receptors in a different manner","volume":"472","author":"Drzazga","year":"2018","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"33833","DOI":"10.1074\/jbc.M109.024869","article-title":"Lysophosphatidylcholine activates adipocyte glucose uptake and lowers blood glucose levels in murine models of diabetes","volume":"284","author":"Yea","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1002\/oby.20960","article-title":"Serum autotaxin is independently associated with hepatic steatosis in women with severe obesity","volume":"23","author":"Rachakonda","year":"2015","journal-title":"Obesity"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1002\/oby.21232","article-title":"Serum Autotaxin\/ENPP2 correlates with insulin resistance in older humans with obesity","volume":"23","author":"Reeves","year":"2015","journal-title":"Obesity"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e14004","DOI":"10.14814\/phy2.14004","article-title":"Acute and chronic effect of bariatric surgery on circulating autotaxin levels","volume":"7","author":"Bourgeois","year":"2019","journal-title":"Physiol. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s00125-004-1660-8","article-title":"Potential involvement of adipocyte insulin resistance in obesity-associated up-regulation of adipocyte lysophospholipase D\/autotaxin expression","volume":"48","author":"Boucher","year":"2005","journal-title":"Diabetologia"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1210\/en.2017-00035","article-title":"Autotaxin Is Regulated by Glucose and Insulin in Adipocytes","volume":"158","author":"Kane","year":"2017","journal-title":"Endocrinology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1194\/jlr.M082008","article-title":"Autotaxin-LPA signaling contributes to obesity-induced insulin resistance in muscle and impairs mitochondrial metabolism","volume":"59","author":"Nzirorera","year":"2018","journal-title":"J. Lipid Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1530\/JME-18-0242","article-title":"Adipose tissue-derived autotaxin causes cardiomyopathy in obese mice","volume":"63","author":"Xu","year":"2019","journal-title":"J. Mol. Endocrinol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4154","DOI":"10.2337\/db13-1694","article-title":"ENPP2 contributes to adipose tissue expansion and insulin resistance in diet-induced obesity","volume":"63","author":"Nishimura","year":"2014","journal-title":"Diabetes"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e97293","DOI":"10.1172\/jci.insight.97293","article-title":"The G\u03b112\/13-coupled receptor LPA4 limits proper adipose tissue expansion and remodeling in diet-induced obesity","volume":"3","author":"Yanagida","year":"2018","journal-title":"JCI Insight"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1096\/fj.201801226R","article-title":"Dexamethasone decreases the autotaxin-lysophosphatidate-inflammatory axis in adipose tissue: Implications for the metabolic syndrome and breast cancer","volume":"33","author":"Meng","year":"2019","journal-title":"FASEB J."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"25823","DOI":"10.1074\/jbc.M116.756908","article-title":"Autotaxin Expression Is Regulated at the Post-transcriptional Level by the RNA-binding Proteins HuR and AUF1","volume":"291","author":"Sun","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"14009","DOI":"10.1074\/jbc.RA119.009002","article-title":"Regulation of PLPP3 gene expression by NF-\u03baB family transcription factors","volume":"294","author":"Mao","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"110793","DOI":"10.1016\/j.mce.2020.110793","article-title":"MicroRNA-184 alleviates insulin resistance in cardiac myocytes and high fat diet-induced cardiac dysfunction in mice through the LPP3\/DAG pathway","volume":"508","author":"Chang","year":"2020","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Murph, M.M. (2019). MicroRNA Regulation of the Autotaxin-Lysophosphatidic Acid Signaling Axis. Cancers, 11.","DOI":"10.3390\/cancers11091369"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"402","DOI":"10.3389\/fendo.2018.00402","article-title":"Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation","volume":"9","author":"Hayder","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1602322","DOI":"10.1183\/13993003.02322-2016","article-title":"Metabolomics analysis identifies sex-associated metabotypes of oxidative stress and the autotaxin-lysoPA axis in COPD","volume":"49","author":"Naz","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1007\/s12020-018-1753-7","article-title":"Exosomal microRNA-29a mediates cardiac dysfunction and mitochondrial inactivity in obesity-related cardiomyopathy","volume":"63","author":"Li","year":"2019","journal-title":"Endocrine"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"53","DOI":"10.2337\/db15-0770","article-title":"The microRNA-29 Family Dictates the Balance Between Homeostatic and Pathological Glucose Handling in Diabetes and Obesity","volume":"65","author":"Dooley","year":"2016","journal-title":"Diabetes"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.bbrc.2019.05.113","article-title":"Adipose tissue macrophage-derived exosomal miR-29a regulates obesity-associated insulin resistance","volume":"515","author":"Liu","year":"2019","journal-title":"Biochem. Biophy. Res. Commun."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1002\/2211-5463.12608","article-title":"Autotaxin is a novel target of microRNA-101-3p","volume":"9","author":"Wang","year":"2019","journal-title":"FEBS Open Bio"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Brandon, J.A., Kraemer, M., Vandra, J., Halder, S., Ubele, M., Morris, A.J., and Smyth, S.S. (2019). Adipose-derived autotaxin regulates inflammation and steatosis associated with diet-induced obesity. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0208099"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1210\/me.2011-1229","article-title":"Autotaxin and its product lysophosphatidic acid suppress brown adipose differentiation and promote diet-induced obesity in mice","volume":"26","author":"Federico","year":"2012","journal-title":"Mol. Endocrinol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"14656","DOI":"10.1074\/jbc.M412585200","article-title":"Lysophosphatidic acid inhibits adipocyte differentiation via lysophosphatidic acid 1 receptor-dependent down-regulation of peroxisome proliferator-activated receptor gamma2","volume":"280","author":"Simon","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/BF03185929","article-title":"Altered food consumption in mice lacking lysophosphatidic acid receptor-1","volume":"65","author":"Dusaulcy","year":"2009","journal-title":"J. Physiol. Biochem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.bbalip.2013.10.003","article-title":"Pro-fibrotic activity of lysophosphatidic acid in adipose tissue: In vivo and in vitro evidence","volume":"1841","author":"Rancoule","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1159\/000362990","article-title":"Divergent role of sphingosine 1-phosphate on insulin resistance","volume":"34","author":"Fayyaz","year":"2014","journal-title":"Cell Physiol. Biochem."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Kowalski, G.M., Carey, A.L., Selathurai, A., Kingwell, B.A., and Bruce, C.R. (2013). Plasma sphingosine-1-phosphate is elevated in obesity. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072449"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Brown, A., Hossain, I., Perez, L.J., Nzirorera, C., Tozer, K., D\u2019Souza, K., Trivedi, P.C., Aguiar, C., Yip, A.M., and Shea, J. (2017). Lysophosphatidic acid receptor mRNA levels in heart and white adipose tissue are associated with obesity in mice and humans. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0189402"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"108809","DOI":"10.1016\/j.celrep.2021.108809","article-title":"Atx regulates skeletal muscle regeneration via LPAR1 and promotes hypertrophy","volume":"34","author":"Ray","year":"2021","journal-title":"Cell Rep."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.yjmcc.2003.12.010","article-title":"Lysophosphatidic acid induces hypertrophy of neonatal cardiac myocytes via activation of Gi and Rho","volume":"36","author":"Means","year":"2004","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.3389\/fphys.2018.01315","article-title":"Lysophosphatidic Acid Is Associated With Cardiac Dysfunction and Hypertrophy by Suppressing Autophagy via the LPA3\/AKT\/mTOR Pathway","volume":"9","author":"Yang","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"22550","DOI":"10.18632\/oncotarget.15123","article-title":"Diet-induced obesity links to ER positive breast cancer progression via LPA\/PKD-1-CD36 signaling-mediated microvascular remodeling","volume":"8","author":"Dong","year":"2017","journal-title":"Oncotarget"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41392-020-00367-5","article-title":"Role of lysophosphatidic acid and its receptors in health and disease: Novel therapeutic strategies","volume":"6","author":"Geraldo","year":"2021","journal-title":"Signal. Transduct. Target. Ther."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Benesch, M.G.K., MacIntyre, I.T.K., McMullen, T.P.W., and Brindley, D.N. (2018). Coming of Age for Autotaxin and Lysophosphatidate Signaling: Clinical Applications for Preventing, Detecting and Targeting Tumor-Promoting Inflammation. 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