Disclosure: None of the authors declares conflict of interest.
Comparison of in vivo effects of insulin on SREBP-1c activation and INSIG-1/2 in rat liver and human and rat adipose tissue
Article first published online: 26 JUL 2013
Copyright © 2012 The Obesity Society
Volume 21, Issue 6, pages 1208–1214, June 2013
How to Cite
Boden, G., Salehi, S., Cheung, P., Homko, C., Song, W., Loveland-Jones, C. and Jayarajan, S. (2013), Comparison of in vivo effects of insulin on SREBP-1c activation and INSIG-1/2 in rat liver and human and rat adipose tissue. Obesity, 21: 1208–1214. doi: 10.1002/oby.20134
Funding agencies: This work was supported by the National Institutes of Health (grants R01-DK090588 and R01-HL073367) and the American Diabetes Association (grant 1-10-CT-06) (all to G.B.).
- Issue published online: 26 JUL 2013
- Article first published online: 26 JUL 2013
- Accepted manuscript online: 6 NOV 2012 08:13AM EST
- Manuscript Accepted: SEP 2012
- Manuscript Received: APR 2012
The stimulatory effects of insulin on de novo lipogenesis (DNL) in the liver, where it is an important contributor to non-alcoholic fatty liver disease (NAFLD), hepatic and systemic insulin resistance, is strong and well established. In contrast, insulin plays only a minor role in DNL in adipose tissue. The reason why insulin stimulates DNL more in liver than in fat is not known but may be due to differential regulation of the transcription and post-translational activation of sterol regulatory element binding proteins (SREBPs). To test this hypothesis, we have examined effects of insulin on activation of SREBP-1c in liver of rats and in adipose tissue of rats and human subjects.
Design and Methods
Liver and epidydimal fat were obtained from alert rats and subcutaneous adipose tissue from human subjects in response to 4 h euglycemic-hyperinsulinemic clamps.
Here we show that acutely raising plasma insulin levels in rats and humans increased SREBP-1 mRNA comparably 3-4 fold in rat liver and rat and human adipose tissue, but increased post-translational activation of SREBP-1c only in rat liver, while decreasing it in adipose tissue. These differential effects of insulin on SREBP-1c activation in liver and adipose tissue were associated with robust changes in the opposite direction of INSIG-1 and to a lesser extent of INSIG-2 mRNA and proteins.
We conclude that these findings support the hypothesis that insulin stimulated activation of SREBP-1c in the liver, at least in part, by suppressing INSIG-1 and -2, whereas in adipose tissue, an increase in INSIG-1 and -2 prevented SREBP-1c activation.