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

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
• phosphatidylinositol 3 kinase
• mitochondria uncoupled protein2

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by grants from KAKENHI [18K14968 to Y.W., 18K11093 to T.T., 16K08290 to K.M.], the Smoking Research Foundation, the MWU Bioscience Research Centre (to K.M.), the Nakatomi Foundation (to K.F.), the TANITA Healthy Weight Community Trust (to K.F.), and the Foundation for Growth Science (to K.M., K. F.).