Nuclear receptor cofactor receptor interacting protein 140 controls hepatic triglyceride metabolism during wasting in mice

Authors

  • Mauricio Berriel Diaz,

    1. Emmy Noether and Marie Curie Research Group, Molecular Metabolic Control, German Cancer Research Center Heidelberg, Heidelberg, Germany
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  • Anja Krones-Herzig,

    1. Emmy Noether and Marie Curie Research Group, Molecular Metabolic Control, German Cancer Research Center Heidelberg, Heidelberg, Germany
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  • Dagmar Metzger,

    1. Emmy Noether and Marie Curie Research Group, Molecular Metabolic Control, German Cancer Research Center Heidelberg, Heidelberg, Germany
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  • Anja Ziegler,

    1. Emmy Noether and Marie Curie Research Group, Molecular Metabolic Control, German Cancer Research Center Heidelberg, Heidelberg, Germany
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  • Alexandros Vegiopoulos,

    1. Emmy Noether and Marie Curie Research Group, Molecular Metabolic Control, German Cancer Research Center Heidelberg, Heidelberg, Germany
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  • Martin Klingenspor,

    1. Technical University Munich, Department of Molecular Nutritional Medicine, Freising-Weihenstephan, Germany
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  • Karin Müller-Decker,

    1. Core Facility Tumor Models, German Cancer Research Center Heidelberg, Heidelberg, Germany
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  • Stephan Herzig

    Corresponding author
    1. Emmy Noether and Marie Curie Research Group, Molecular Metabolic Control, German Cancer Research Center Heidelberg, Heidelberg, Germany
    • Molecular Metabolic Control, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
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    • fax: (49) 6221-423595.


  • Potential conflict of interest: Nothing to report.

Abstract

In mammals, triglycerides (TG) represent the most concentrated form of energy. Aberrant TG storage and availability are intimately linked to the negative energy balance under severe clinical conditions, such as starvation, sepsis, or cancer cachexia. Despite its crucial role for energy homeostasis, molecular key determinants of TG metabolism remain enigmatic. Here we show that the expression of nuclear receptor cofactor receptor interacting protein (RIP) 140 was induced in livers of starved, septic, and tumor-bearing mice. Liver-specific knockdown of RIP140 led to increased hepatic TG release and alleviated hepatic steatosis in tumor-bearing, cachectic animals. Indeed, hepatic RIP140 was found to control the expression of lipid-metabolizing genes in liver. Conclusion: By preventing the mobilization of hepatic TG stores, the induction of RIP140 in liver provides a molecular rationale for hepatic steatosis in starvation, sepsis, or cancer cachexia. Inhibition of hepatic RIP140 transcriptional activity might, thereby, provide an attractive adjunct scheme in the treatment of these conditions. (HEPATOLOGY 2008.)

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