Lysophosphatidic Acid Signaling in Obesity and Insulin Resistance

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

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.

Publication types

  • Review

MeSH terms

  • Adipocytes / drug effects
  • Adipocytes / metabolism*
  • Adipocytes / pathology
  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Anti-Obesity Agents / therapeutic use
  • Blood Glucose / metabolism
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / etiology
  • Humans
  • Insulin / blood
  • Insulin Resistance*
  • Lysophospholipids / blood*
  • Molecular Targeted Therapy
  • Obesity / blood*
  • Obesity / complications
  • Obesity / drug therapy
  • Obesity / physiopathology
  • Phosphoric Diester Hydrolases / metabolism
  • Receptors, Lysophosphatidic Acid / drug effects
  • Receptors, Lysophosphatidic Acid / metabolism*
  • Risk Factors
  • Signal Transduction*

Substances

  • Anti-Inflammatory Agents
  • Anti-Obesity Agents
  • Blood Glucose
  • Insulin
  • Lysophospholipids
  • Receptors, Lysophosphatidic Acid
  • Phosphoric Diester Hydrolases
  • alkylglycerophosphoethanolamine phosphodiesterase
  • lysophosphatidic acid