Impact of silencing hepatic SREBP-1 on insulin signaling

Victoria Jideonwo, Yongyong Hou, Miwon Ahn, Sneha Surendran, Nuria Morral

Research output: Contribution to journalArticle

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Abstract

Sterol Regulatory Element Binding Protein-1 (SREBP-1) is a conserved transcription factor of the basic helix-loop-helix leucine zipper family (bHLH-Zip) that plays a central role in regulating expression of genes of carbohydrate and fatty acid metabolism in the liver. SREBP-1 activity is essential for the control of insulin-induced anabolic processes during the fed state. In addition, SREBP-1 regulates expression of key molecules in the insulin signaling pathway, including insulin receptor substrate 2 (IRS2) and a subunit of the phosphatidylinositol 3-kinase (PI3K) complex, PIK3R3, suggesting that feedback mechanisms exist between SREBP-1 and this pathway. Nevertheless, the overall contribution of SREBP-1 activity to maintain insulin signal transduction is unknown. Furthermore, Akt is a known activator of mTORC1, a sensor of energy availability that plays a fundamental role in metabolism, cellular growth and survival. We have silenced SREBP-1 and explored the impact on insulin signaling and mTOR in mice under fed, fasted and refed conditions. No alterations in circulating levels of insulin were observed. The studies revealed that depletion of SREBP-1 had no impact on IRS1Y612, AktS473, and downstream effectors GSK3αS21 and FoxO1S256 during the fed state. Nevertheless, reduced levels of these molecules were observed under fasting conditions. These effects were not associated with changes in phosphorylation of mTOR. Overall, our data indicate that the contribution of SREBP-1 to maintain insulin signal transduction in liver is modest.

Original languageEnglish (US)
Article numbere0196704
JournalPLoS One
Volume13
Issue number5
DOIs
StatePublished - May 1 2018

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Sterol Regulatory Element Binding Protein 1
sterols
binding proteins
insulin
Insulin
liver
Liver
Signal transduction
Metabolism
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
signal transduction
Signal Transduction
Phosphatidylinositol 3-Kinase
basic helix-loop-helix transcription factors
Insulin Receptor Substrate Proteins
leucine zipper
Phosphorylation
Molecules
fatty acid metabolism
phosphatidylinositol 3-kinase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Impact of silencing hepatic SREBP-1 on insulin signaling. / Jideonwo, Victoria; Hou, Yongyong; Ahn, Miwon; Surendran, Sneha; Morral, Nuria.

In: PLoS One, Vol. 13, No. 5, e0196704, 01.05.2018.

Research output: Contribution to journalArticle

Jideonwo, V, Hou, Y, Ahn, M, Surendran, S & Morral, N 2018, 'Impact of silencing hepatic SREBP-1 on insulin signaling', PLoS One, vol. 13, no. 5, e0196704. https://doi.org/10.1371/journal.pone.0196704
Jideonwo, Victoria ; Hou, Yongyong ; Ahn, Miwon ; Surendran, Sneha ; Morral, Nuria. / Impact of silencing hepatic SREBP-1 on insulin signaling. In: PLoS One. 2018 ; Vol. 13, No. 5.
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