Hepatic-specific activation of peroxisome proliferator-activated receptor γ coactivator-1β protects against steatohepatitis

Authors

  • Elena Bellafante,

    1. Laboratory of Lipid Metabolism and Cancer, Department of Translational Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro (CH), Italy
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  • Stefania Murzilli,

    1. Laboratory of Lipid Metabolism and Cancer, Department of Translational Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro (CH), Italy
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  • Lorena Salvatore,

    1. Laboratory of Lipid Metabolism and Cancer, Department of Translational Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro (CH), Italy
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  • Dominga Latorre,

    1. Department of Basic Medical Sciences, Neurosciences and Sense-organs, Biochemistry, Aldo Moro University of Bari, Italy
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  • Gaetano Villani,

    1. Department of Basic Medical Sciences, Neurosciences and Sense-organs, Biochemistry, Aldo Moro University of Bari, Italy
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  • Antonio Moschetta

    Corresponding author
    1. Laboratory of Lipid Metabolism and Cancer, Department of Translational Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro (CH), Italy
    2. Clinica Medica “A. Murri,” Interdisciplinar Department of Medicine, University of Bari, Italy
    3. National Cancer Institute Giovanni Paolo II, Bari, Italy
    4. National Institute for Digestive Diseases, IRCCS “S. de Bellis,” Castellana Grotte, Bari Italy
    • University of Bari, Consorzio Mario Negri Sud, Via Nazionale 8A, 66030 Santa Maria Imbaro (Chieti), Italy===

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    • fax: +39-0872-570299


  • Potential conflict of interest: Nothing to report.

  • View this article online at wileyonlinelibrary.com.

Abstract

Development of hepatic steatosis and its progression to steatohepatitis may be the consequence of dysfunction of several metabolic pathways, such as triglyceride synthesis, very low-density lipoprotein (VLDL) secretion, and fatty acid β-oxidation. Peroxisome proliferator-activated receptor γ coactivator-1β (PGC-1β) is a master regulator of mitochondrial biogenesis and oxidative metabolism, lipogenesis, and triglyceride (TG) secretion. Here we generated a novel mouse model with constitutive hepatic activation of PGC-1β and studied the role of this transcriptional coactivator in dietary-induced steatosis and steatohepatitis. Selective activation of PGC-1β within hepatocytes is able to protect the liver from lipid overload and from progression to fibrosis. The protective function exerted by PGC-1β is due to its ability to induce mitochondrial oxidative phosphorylation, fatty acid β-oxidation, and citrate cycle, as well as to decrease oxidative stress and promote TG secretion in the blood stream. These findings bolster the concept that a combined hepatic specific action of PGC-1β on lipid synthesis and secretion, as well as on mitochondrial biogenesis and function, could protect against steatohepatitis. (HEPATOLOGY 2013)

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