Regulation of IGFBP-2 expression during fasting

Hye Suk Kang, Mi Young Kim, Seung Jae Kim, Jae Ho Lee, Yong Deuk Kim, Young Kyo Seo, Jae Hoon Bae, Goo Taeg Oh, Dae Kyu Song, Yong Ho Ahn, Seung Soon Im

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2), one of the most abundant circulating IGFBPs, is known to attenuate the biological action of IGF-1. Although the effect of IGFBP-2 in preventing metabolic disorders is well known, its regulatory mechanism remains unclear. In the present study, we demonstrated the transcriptional regulation of the Igfbp-2 gene by peroxisome-proliferator-activated receptor (PPAR) α in the liver. During fasting, both Igfbp-2 and PPARα expression levels were increased. Wy14643, a selective PPARα agonist, significantly induced Igfbp-2 gene expression in primary cultured hepatocytes. However, Igfbp-2 gene expression in Pparα null micewas not affected by fasting orWy14643. In addition, through transient transfection and chromatin immunoprecipitation assay in fasted livers, we determined that PPARα bound to the putative PPAR-responsive element between - 511 bp and - 499 bp on the Igfbp-2 gene promoter, indicating that the Igfbp-2 gene transcription is activated directly by PPARα . To explore the role of PPARα in IGF-1 signalling, we treated primary cultured hepatocytes with Wy14643 and observed a decrease in the number of IGF-1 receptors (IGF-1Rs) and in Akt phosphorylation. No inhibition was observed in the hepatocytes isolated from Pparα null mice. These results suggest that PPARα controls IGF-1 signalling through the up-regulation of hepatic Igfbp-2 transcription during fasting and Wy14643 treatment.

Original languageEnglish
Pages (from-to)453-460
Number of pages8
JournalBiochemical Journal
Volume467
Issue number3
DOIs
StatePublished - 1 May 2015

Keywords

  • Fasting
  • Gene expression
  • Insulin-like growth factor-1 (IGF-1)
  • Insulin-like growth factor-binding protein 2 (IGFBP-2)
  • Liver
  • Peroxisome-proliferator-activated receptor α (PPARα)

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