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Impact of silencing hepatic SREBP-1 on insulin signaling

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 f...

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Autores principales: Jideonwo, Victoria, Hou, Yongyong, Ahn, Miwon, Surendran, Sneha, Morral, Núria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933792/
https://www.ncbi.nlm.nih.gov/pubmed/29723221
http://dx.doi.org/10.1371/journal.pone.0196704
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author Jideonwo, Victoria
Hou, Yongyong
Ahn, Miwon
Surendran, Sneha
Morral, Núria
author_facet Jideonwo, Victoria
Hou, Yongyong
Ahn, Miwon
Surendran, Sneha
Morral, Núria
author_sort Jideonwo, Victoria
collection PubMed
description 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 IRS1(Y612), Akt(S473), and downstream effectors GSK3α(S21) and FoxO1(S256) 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.
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spelling pubmed-59337922018-05-18 Impact of silencing hepatic SREBP-1 on insulin signaling Jideonwo, Victoria Hou, Yongyong Ahn, Miwon Surendran, Sneha Morral, Núria PLoS One Research Article 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 IRS1(Y612), Akt(S473), and downstream effectors GSK3α(S21) and FoxO1(S256) 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. Public Library of Science 2018-05-03 /pmc/articles/PMC5933792/ /pubmed/29723221 http://dx.doi.org/10.1371/journal.pone.0196704 Text en © 2018 Jideonwo et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Jideonwo, Victoria
Hou, Yongyong
Ahn, Miwon
Surendran, Sneha
Morral, Núria
Impact of silencing hepatic SREBP-1 on insulin signaling
title Impact of silencing hepatic SREBP-1 on insulin signaling
title_full Impact of silencing hepatic SREBP-1 on insulin signaling
title_fullStr Impact of silencing hepatic SREBP-1 on insulin signaling
title_full_unstemmed Impact of silencing hepatic SREBP-1 on insulin signaling
title_short Impact of silencing hepatic SREBP-1 on insulin signaling
title_sort impact of silencing hepatic srebp-1 on insulin signaling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933792/
https://www.ncbi.nlm.nih.gov/pubmed/29723221
http://dx.doi.org/10.1371/journal.pone.0196704
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