Projects per year
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.
Original language | English |
---|---|
Pages (from-to) | 1078 - 1089 |
Number of pages | 12 |
Journal | Cell Metabolism |
Volume | 22 |
Issue number | 6 |
DOIs | |
Publication status | Published - 2015 |
Projects
- 3 Finished
-
Altered protein secretion links the fatty liver to metabolic disease
National Health and Medical Research Council (NHMRC) (Australia)
1/01/14 → 31/12/16
Project: Research
-
The role of circulating ceramides in insulin resistance and obesity
Hoy, A.
National Health and Medical Research Council (NHMRC) (Australia)
1/01/10 → 31/12/13
Project: Research
-
NHMRC Research Fellowship
National Health and Medical Research Council (NHMRC) (Australia)
1/01/10 → 31/12/19
Project: Research