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

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 languageEnglish (US)
Article number9958
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Sterol Regulatory Element Binding Protein 1
PPAR alpha
Sterol Regulatory Element Binding Proteins
Fasting
Liver
Fatty Acids
Gene Expression
Lipogenesis
Trans-Activators
Chromatin Immunoprecipitation
Golgi Apparatus
Protein Transport
Starvation
Transfection
Hepatocytes
Homeostasis
Cholesterol
Insulin
Food
Messenger RNA

ASJC Scopus subject areas

  • General

Cite this

Lee, J. H., Kang, H. S., Park, H. Y., Moon, Y. A., Kang, Y. N., Oh, B. C., ... Im, S. S. (2017). PPARα-dependent Insig2a overexpression inhibits SREBP-1c processing during fasting. Scientific Reports, 7(1), [9958]. https://doi.org/10.1038/s41598-017-10523-7

PPARα-dependent Insig2a overexpression inhibits SREBP-1c processing during fasting. / Lee, Jae Ho; Kang, Hye Suk; Park, Hyeon Young; Moon, Young Ah; Kang, Yu Na; Oh, Byung Chul; Song, Dae Kyu; Bae, Jae Hoon; Im, Seung Soon.

In: Scientific Reports, Vol. 7, No. 1, 9958, 01.12.2017.

Research output: Contribution to journalArticle

Lee, JH, Kang, HS, Park, HY, Moon, YA, Kang, YN, Oh, BC, Song, DK, Bae, JH & Im, SS 2017, 'PPARα-dependent Insig2a overexpression inhibits SREBP-1c processing during fasting', Scientific Reports, vol. 7, no. 1, 9958. https://doi.org/10.1038/s41598-017-10523-7
Lee, Jae Ho ; Kang, Hye Suk ; Park, Hyeon Young ; Moon, Young Ah ; Kang, Yu Na ; Oh, Byung Chul ; Song, Dae Kyu ; Bae, Jae Hoon ; Im, Seung Soon. / PPARα-dependent Insig2a overexpression inhibits SREBP-1c processing during fasting. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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