Comparison of in vivo effects of insulin on SREBP-1c activation and INSIG-1/2 in rat liver and human and rat adipose tissue

Authors

  • Guenther Boden,

    Corresponding author
    1. Division of Endocrinology/Diabetes/Metabolism, Clinical Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
    • Division of Endocrinology/Diabetes/Metabolism, Clinical Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA. E-mail: bodengh@tuhs.temple.edu

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  • Sajad Salehi,

    1. Division of Endocrinology/Diabetes/Metabolism, Clinical Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
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  • Peter Cheung,

    1. Division of Endocrinology/Diabetes/Metabolism, Clinical Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
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  • Carol Homko,

    1. Division of Endocrinology/Diabetes/Metabolism, Clinical Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
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  • Weiwei Song,

    1. Division of Endocrinology/Diabetes/Metabolism, Clinical Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
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  • Catherine Loveland-Jones,

    1. Department of Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
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  • Senthil Jayarajan

    1. Department of Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania, USA
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  • Disclosure: None of the authors declares conflict of interest.

  • 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.).

Abstract

Objective

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.

Results

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.

Conclusions

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.

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