Fetuin B is a secreted hepatocyte factor linking steatosis to impaired glucose metabolism

Meex, Ruth C., Hoy, Andrew J., Morris, Alexander, Brown, Russell D., Lo, Jennifer C. Y., Burke, Melissa, Goode, Robert J.A., Kingwell, Bronwyn A., Kraakman, Michael J., Febbraio, Mark A., Greve, Jan Willem, Rensen, Sander S., Molloy, Mark P., Lancaster, Graeme I., Bruce, Clinton R. and Watt, Matthew J. 2015, Fetuin B is a secreted hepatocyte factor linking steatosis to impaired glucose metabolism, Cell metabolism, vol. 22, no. 6, pp. 1078-1089, doi: 10.1016/j.cmet.2015.09.023.

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Title Fetuin B is a secreted hepatocyte factor linking steatosis to impaired glucose metabolism
Author(s) Meex, Ruth C.
Hoy, Andrew J.
Morris, Alexander
Brown, Russell D.
Lo, Jennifer C. Y.
Burke, Melissa
Goode, Robert J.A.
Kingwell, Bronwyn A.
Kraakman, Michael J.
Febbraio, Mark A.
Greve, Jan Willem
Rensen, Sander S.
Molloy, Mark P.
Lancaster, Graeme I.
Bruce, Clinton R.ORCID iD for Bruce, Clinton R. orcid.org/0000-0002-0515-3343
Watt, Matthew J.
Journal name Cell metabolism
Volume number 22
Issue number 6
Start page 1078
End page 1089
Total pages 13
Publisher Cell Press
Place of publication St. Louis, M. O.
Publication date 2015-12
ISSN 1550-4131
Summary  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. Meex et al. use proteomic approaches to identify steatosis as a factor that changes protein secretion in hepatocytes. Secreted factors from steatotic hepatocytes caused insulin resistance and inflammation. One secreted protein, fetuin B, was identified as a hepatokine that is increased in type 2 diabetes and causes impaired glucose metabolism.
Language eng
DOI 10.1016/j.cmet.2015.09.023
Field of Research 0601 Biochemistry And Cell Biology
1101 Medical Biochemistry And Metabolomics
110199 Medical Biochemistry and Metabolomics not elsewhere classified
Socio Economic Objective 920104 Diabetes
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, Cell Press
Persistent URL http://hdl.handle.net/10536/DRO/DU:30079808

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