Monocyte chemoattractant protein-1 secreted by adipose tissue induces direct lipid accumulation in hepatocytes

Authors

  • Sophie Clément,

    Corresponding author
    1. Division of Clinical Pathology, Geneva University Hospital, University of Geneva, Geneva, Switzerland
    • Department of Clinical Pathology, University Hospital, 1 rue Michel Servet, 1211 Geneva 4, Switzerland
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    • fax: (41) 22 3724920

  • Cristiana Juge-Aubry,

    1. Laboratory of Molecular Endocrinology, Departments of Medicine and of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland
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  • Antonino Sgroi,

    1. Surgical Research Unit, Department of Surgery, Geneva University Hospital, University of Geneva, Geneva, Switzerland
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  • Stéphanie Conzelmann,

    1. Division of Clinical Pathology, Geneva University Hospital, University of Geneva, Geneva, Switzerland
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  • Valerio Pazienza,

    1. Division of Clinical Pathology, Geneva University Hospital, University of Geneva, Geneva, Switzerland
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  • Brigitte Pittet-Cuenod,

    1. Division of Plastic and Reconstructive Surgery, Geneva University Hospital, University of Geneva, Geneva, Switzerland
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  • Christoph A. Meier,

    1. Laboratory of Molecular Endocrinology, Departments of Medicine and of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland
    2. Department of Medicine, Triemli Hospital, Zurich, Switzerland
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  • Francesco Negro

    1. Division of Clinical Pathology, Geneva University Hospital, University of Geneva, Geneva, Switzerland
    2. Division of Gastroenterology and Hepatology, Geneva University Hospital, University of Geneva, Geneva, Switzerland
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  • Potential conflict of interest: Nothing to report.

Abstract

For many years, adipose tissue has been mainly considered as an inert reservoir for storing triglycerides. Since the discovery that adipocytes may secrete a variety of bioactive molecules (hormones, chemokines, and cytokines), an endocrine and paracrine role for white adipose tissue (WAT) in the regulation of energy balance and other physiological processes has been established, particularly with regard to brain and muscle. In contrast, little is known about the interactions of WAT with liver. Hence, we examined the effect of the secretory products of WAT on hepatocytes. Conditioned medium of human WAT explants induced significant steatosis in hepatocyte cell lines. Factor(s) responsible for the conditioned medium-induced steatosis were screened by a battery of blocking antibodies against different cytokines/chemokines shown to be secreted by WAT. In contrast to interleukin-8 and interleukin-6, the monocyte chemoattractant protein-1 was capable of inducing steatosis in hepatocytes in a time-dependent manner at concentrations similar to those found in conditioned medium. Incubation of conditioned medium with antimonocyte chemoattractant protein-1 antibodies prevented triglyceride accumulation. Investigation of the mechanism leading to the triglyceride accumulation showed that both a diminution of apolipoprotein B secretion and an increase in phosphoenolpyruvate carboxykinase messenger RNA may be involved. Conclusion: The monocyte chemoattractant protein-1 secreted by adipose tissue may induce steatosis not only recruiting macrophages but also acting directly on hepatocytes. (HEPATOLOGY 2008.)

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