PPARα-dependent Insig2a overexpression inhibits SREBP-1c processing during fasting

Jae Ho Lee; Hye Suk Kang; Hyeon Young Park; Young Ah Moon; Yu Na Kang; Byung Chul Oh; Dae Kyu Song; Jae Hoon Bae; Seung Soon Im

doi:10.1038/s41598-017-10523-7

PPARα-dependent Insig2a overexpression inhibits SREBP-1c processing during fasting

Jae Ho Lee, Hye Suk Kang, Hyeon Young Park, Young Ah Moon, Yu Na Kang, Byung Chul Oh, Dae Kyu Song, Jae Hoon Bae, Seung Soon Im

Molecular Genetics

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

Abstract

Peroxisome-proliferator-activated receptor alpha (PPARα) and sterol regulatory element-binding protein (SREBP) play a role in regulating cellular fatty acid and cholesterol homeostasis via fatty acid oxidation and lipogenesis. The control of SREBP processing is regulated by the insulin induced gene (INSIG)2a protein, which binds SREBP to prevent SREBP translocation to the Golgi apparatus during nutrient starvation in the liver. However, the regulation of SREBP-1c processing by INSIGs during fasting and the regulatory mechanisms of the mouse Insig2a gene expression have not been clearly addressed. In the present study, we found that Insig2a was upregulated by PPARα in mouse livers and primary hepatocytes during fasting, whereas Insig2a mRNA expression was decreased in the livers of refed mice. A PPAR-responsive element between -126 bp and -114 bp in the Insig2a promoter was identified by a transient transfection assay and a chromatin immunoprecipitation assay; its role in regulation by PPARα was characterised using Pparα-null mice. These results suggest that PPARα is a trans-acting factor that enhances Insig2a gene expression, thereby suppressing SREBP-1c processing during fasting.

Original language	English (US)
Article number	9958
Journal	Scientific reports
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41598-017-10523-7
State	Published - Dec 1 2017

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@article{143e6846978a4b928fa8e9f28ecf3776,

title = "PPARα-dependent Insig2a overexpression inhibits SREBP-1c processing during fasting",

abstract = "Peroxisome-proliferator-activated receptor alpha (PPARα) and sterol regulatory element-binding protein (SREBP) play a role in regulating cellular fatty acid and cholesterol homeostasis via fatty acid oxidation and lipogenesis. The control of SREBP processing is regulated by the insulin induced gene (INSIG)2a protein, which binds SREBP to prevent SREBP translocation to the Golgi apparatus during nutrient starvation in the liver. However, the regulation of SREBP-1c processing by INSIGs during fasting and the regulatory mechanisms of the mouse Insig2a gene expression have not been clearly addressed. In the present study, we found that Insig2a was upregulated by PPARα in mouse livers and primary hepatocytes during fasting, whereas Insig2a mRNA expression was decreased in the livers of refed mice. A PPAR-responsive element between -126 bp and -114 bp in the Insig2a promoter was identified by a transient transfection assay and a chromatin immunoprecipitation assay; its role in regulation by PPARα was characterised using Pparα-null mice. These results suggest that PPARα is a trans-acting factor that enhances Insig2a gene expression, thereby suppressing SREBP-1c processing during fasting.",

author = "Lee, {Jae Ho} and Kang, {Hye Suk} and Park, {Hyeon Young} and Moon, {Young Ah} and Kang, {Yu Na} and Oh, {Byung Chul} and Song, {Dae Kyu} and Bae, {Jae Hoon} and Im, {Seung Soon}",

note = "Funding Information: The authors thank Dr. Goo-Tae Oh (Ewha Women University) for providing Pparα-null mice, as well as Dr. Timothy F. Osborne (Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL, USA) and Dr. Baoliang Song (College of Life Sciences, Wuhan University, Wuhan, China) for sharing antibodies and adenovirus. This study was supported by grants from the Korea Research Foundation, Medical Research Center (2014R1A5A2010008), an NRF grant funded by the Korean Government (MSIP) (2016R1A2B4008516), and the Korea Mouse Phenotyping Project (2013M3A9D5072550) of the Ministry of Science, ICT, and Future Planning through the National Research Foundation. Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

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doi = "10.1038/s41598-017-10523-7",

language = "English (US)",

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T1 - PPARα-dependent Insig2a overexpression inhibits SREBP-1c processing during fasting

AU - Lee, Jae Ho

AU - Kang, Hye Suk

AU - Park, Hyeon Young

AU - Moon, Young Ah

AU - Kang, Yu Na

AU - Oh, Byung Chul

AU - Song, Dae Kyu

AU - Bae, Jae Hoon

AU - Im, Seung Soon

N1 - Funding Information: The authors thank Dr. Goo-Tae Oh (Ewha Women University) for providing Pparα-null mice, as well as Dr. Timothy F. Osborne (Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL, USA) and Dr. Baoliang Song (College of Life Sciences, Wuhan University, Wuhan, China) for sharing antibodies and adenovirus. This study was supported by grants from the Korea Research Foundation, Medical Research Center (2014R1A5A2010008), an NRF grant funded by the Korean Government (MSIP) (2016R1A2B4008516), and the Korea Mouse Phenotyping Project (2013M3A9D5072550) of the Ministry of Science, ICT, and Future Planning through the National Research Foundation. Publisher Copyright: © 2017 The Author(s).

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Peroxisome-proliferator-activated receptor alpha (PPARα) and sterol regulatory element-binding protein (SREBP) play a role in regulating cellular fatty acid and cholesterol homeostasis via fatty acid oxidation and lipogenesis. The control of SREBP processing is regulated by the insulin induced gene (INSIG)2a protein, which binds SREBP to prevent SREBP translocation to the Golgi apparatus during nutrient starvation in the liver. However, the regulation of SREBP-1c processing by INSIGs during fasting and the regulatory mechanisms of the mouse Insig2a gene expression have not been clearly addressed. In the present study, we found that Insig2a was upregulated by PPARα in mouse livers and primary hepatocytes during fasting, whereas Insig2a mRNA expression was decreased in the livers of refed mice. A PPAR-responsive element between -126 bp and -114 bp in the Insig2a promoter was identified by a transient transfection assay and a chromatin immunoprecipitation assay; its role in regulation by PPARα was characterised using Pparα-null mice. These results suggest that PPARα is a trans-acting factor that enhances Insig2a gene expression, thereby suppressing SREBP-1c processing during fasting.

AB - Peroxisome-proliferator-activated receptor alpha (PPARα) and sterol regulatory element-binding protein (SREBP) play a role in regulating cellular fatty acid and cholesterol homeostasis via fatty acid oxidation and lipogenesis. The control of SREBP processing is regulated by the insulin induced gene (INSIG)2a protein, which binds SREBP to prevent SREBP translocation to the Golgi apparatus during nutrient starvation in the liver. However, the regulation of SREBP-1c processing by INSIGs during fasting and the regulatory mechanisms of the mouse Insig2a gene expression have not been clearly addressed. In the present study, we found that Insig2a was upregulated by PPARα in mouse livers and primary hepatocytes during fasting, whereas Insig2a mRNA expression was decreased in the livers of refed mice. A PPAR-responsive element between -126 bp and -114 bp in the Insig2a promoter was identified by a transient transfection assay and a chromatin immunoprecipitation assay; its role in regulation by PPARα was characterised using Pparα-null mice. These results suggest that PPARα is a trans-acting factor that enhances Insig2a gene expression, thereby suppressing SREBP-1c processing during fasting.

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JO - Scientific reports

JF - Scientific reports

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PPARα-dependent Insig2a overexpression inhibits SREBP-1c processing during fasting

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