D-chiro-inositol glycan reduces food intake by regulating hypothalamic neuropeptide expression via AKT-FoxO1 pathway

Yoonjeong Jeon, Susan Aja, Gabriele V. Ronnett, Eun Kyoung Kim

Research output: Contribution to journalArticlepeer-review

Abstract

The regulation of food intake is important for body energy homeostasis. Hypothalamic insulin signaling decreases food intake by upregulating the expression of anorexigenic neuropeptides and downregulating the expression of orexigenic neuropeptides. INS-2, a Mn2+ chelate of 4-O-(2-amino-2-deoxy-β-d-galactopyranosyl)-3-O-methyl-d-chiro-inositol, acts as an insulin mimetic and sensitizer. We found that intracerebroventricular injection of INS-2 decreased body weight and food intake in mice. In hypothalamic neuronal cell lines, INS-2 downregulated the expression of neuropeptide Y (NPY), an orexigenic neuropeptide, but upregulated the expression of proopiomelanocortin (POMC), an anorexigenic neuropeptide, via modulation of the AKT-forkhead box-containing protein-O1 (FoxO1) pathway. Pretreatment of these cells with INS-2 enhanced the action of insulin on downstream signaling, leading to a further decrease in NPY expression and increase in POMC expression. These data indicate that INS-2 reduces food intake by regulating the expression of the hypothalamic neuropeptide genes through the AKT-FoxO1 pathway downstream of insulin.

Original languageEnglish (US)
Pages (from-to)818-823
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume470
Issue number4
DOIs
StatePublished - Feb 19 2016

Keywords

  • Food intake
  • INS-2
  • Neuropeptide Y
  • Proopiomelanocortin

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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