Autotaxin-LPA Signaling Contributes to Obesity-Induced Insulin Resistance in Muscle and Impairs Mitochondrial Metabolism

    August 2018 in “ Journal of Lipid Research ”
    Kenneth D’Souza, Carine Nzirorera, Andrew Cowie, Geena V. Paramel, Purvi Trivedi, Thomas O. Eichmann, Dipsikha Biswas, Mohamed Touaibia, Andrew J. Morris, Vassilis Aidinis, Daniel A. Kane, Thomas Pulinilkunnil, Petra C. Kienesberger
    TLDR Blocking the ATX-LPA pathway may improve insulin sensitivity and mitochondrial function in obesity.
    The study concluded that the autotaxin (ATX)-lysophosphatidic acid (LPA) signaling pathway played a significant role in obesity-induced insulin resistance and impaired mitochondrial metabolism in skeletal muscle. Mice with partial ATX deficiency (ATX+/−) were protected from obesity and systemic insulin resistance when fed a high-fat high-sucrose diet, showing improved insulin signaling and mitochondrial function. In vitro, LPA was found to impair insulin signaling and mitochondrial respiration in muscle cells. These findings suggested that targeting the ATX-LPA pathway could be a potential therapeutic strategy for improving insulin sensitivity and mitochondrial function in obese individuals.
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