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Fetuin B Is a Secreted Hepatocyte Factor Linking Steatosis to Impaired Glucose Metabolism.
- Source :
-
Cell metabolism [Cell Metab] 2015 Dec 01; Vol. 22 (6), pp. 1078-89. Date of Electronic Publication: 2015 Oct 22. - Publication Year :
- 2015
-
Abstract
- 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.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Alanine Transaminase blood
Animals
Aspartate Aminotransferases blood
Cells, Cultured
Diabetes Mellitus, Type 2 complications
Diabetes Mellitus, Type 2 metabolism
Diabetes Mellitus, Type 2 pathology
Diet, High-Fat
Fatty Liver complications
Fatty Liver metabolism
Female
Fetuin-B antagonists & inhibitors
Fetuin-B genetics
Hepatocytes cytology
Hepatocytes metabolism
Humans
I-kappa B Kinase metabolism
Insulin Resistance
JNK Mitogen-Activated Protein Kinases metabolism
Liver enzymology
Liver metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Obese
Middle Aged
RNA Interference
Up-Regulation drug effects
Fatty Liver pathology
Fetuin-B metabolism
Glucose metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-7420
- Volume :
- 22
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cell metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 26603189
- Full Text :
- https://doi.org/10.1016/j.cmet.2015.09.023