Fetuin B Is a Secreted Hepatocyte Factor Linking Steatosis to Impaired Glucose Metabolism

Ruth C. Meex, Andrew J. Hoy, Alexander Morris, Russell D. Brown, Jennifer C Y Lo, Melissa Burke, Robert J A Goode, Bronwyn A. Kingwell, Michael J. Kraakman, Mark A. Febbraio, Jan Willem Greve, Sander S. Rensen, Mark P. Molloy, Graeme I. Lancaster, Clinton R. Bruce, Matthew J. Watt*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    142 Citations (Scopus)


    Liver steatosis is associated with the development of insulin resistance and the pathogenesis of type 2 diabetes. We tested the hypothesis that protein signals originating from steatotic hepatocytes communicate with other cells to modulate metabolic phenotypes. We show that the secreted factors from steatotic hepatocytes induce pro-inflammatory signaling and insulin resistance in cultured cells. Next, we identified 168 hepatokines, of which 32 were differentially secreted in steatotic versus non-steatotic hepatocytes. Targeted analysis showed that fetuin B was increased in humans with liver steatosis and patients with type 2 diabetes. Fetuin B impaired insulin action in myotubes and hepatocytes and caused glucose intolerance in mice. Silencing of fetuin B in obese mice improved glucose tolerance. We conclude that the protein secretory profile of hepatocytes is altered with steatosis and is linked to inflammation and insulin resistance. Therefore, preventing steatosis may limit the development of dysregulated glucose metabolism in settings of overnutrition.

    Original languageEnglish
    Pages (from-to)1078-1089
    Number of pages12
    JournalCell Metabolism
    Issue number6
    Publication statusPublished - 1 Dec 2015


    Dive into the research topics of 'Fetuin B Is a Secreted Hepatocyte Factor Linking Steatosis to Impaired Glucose Metabolism'. Together they form a unique fingerprint.

    Cite this