IGF-1 regulate the expression of uncoupling protein 2 via FOXO1

Growth Factors. 2019 Dec;37(5-6):247-256. doi: 10.1080/08977194.2020.1739032. Epub 2020 Mar 10.

Abstract

Mitochondria uncoupling protein2 (UCP2) expressed ubiquitously is a key molecule of energy metabolism. Insulin-like growth factor-1 (IGF-1) is a hormone, a target molecule of growth hormone (GH) signal pathway, which is also known as the drug "mecasermin" for clinical usages. IGF-1 is seemed to be closely related to metabolic diseases, such as adult GH deficiency. However, there has not been reports depicted possible relationship with each other. So, we sought to elucidate the mechanisms by which expression of UCP2 is regulated by IGF-1 via FOXO1. The findings suggested that three sequences in the consensus UCP2 promoter play complementary functional roles in the functional expression of FOXO1. So, we found that FOXO1 is involved in IGF-1-mediated energy metabolism greater than that of direct action of GH via STAT5. Our findings suggested that IGF-1 was involved in energy metabolism by regulating the expression of UCP2 via the PI3K/Akt/FOXO1 pathway.

Keywords: Growth hormone; insulin-like growth factor-1; mitochondria uncoupled protein2; phosphatidylinositol 3 kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipose Tissue / metabolism
  • Animals
  • Energy Metabolism
  • Forkhead Box Protein O1 / metabolism*
  • Gene Expression Regulation
  • Growth Hormone / metabolism*
  • HEK293 Cells
  • Hep G2 Cells
  • Humans
  • Insulin-Like Growth Factor I / metabolism*
  • Mice
  • Mitochondria / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Promoter Regions, Genetic
  • Receptor, IGF Type 1 / metabolism
  • STAT5 Transcription Factor / metabolism
  • Tumor Suppressor Proteins / metabolism
  • Uncoupling Protein 2 / metabolism*

Substances

  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • Foxo1 protein, mouse
  • IGF1 protein, human
  • IGF1R protein, human
  • Igf1r protein, mouse
  • STAT5 Transcription Factor
  • STAT5A protein, human
  • Stat5a protein, mouse
  • Tumor Suppressor Proteins
  • UCP2 protein, human
  • Ucp2 protein, mouse
  • Uncoupling Protein 2
  • insulin-like growth factor-1, mouse
  • Insulin-Like Growth Factor I
  • Growth Hormone
  • Receptor, IGF Type 1