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D-chiro-inositol glycan reduces food intake by regulating hypothalamic neuropeptide expression via AKT-FoxO1 pathway
- D-chiro-inositol glycan reduces food intake by regulating hypothalamic neuropeptide expression via AKT-FoxO1 pathway
- Jeon, Y[Jeon, Yoonjeong]; Aja, S[Aja, Susan]; Ronnett, GV[Ronnett, Gabriele V.]; Kim, EK[Kim, Eun-Kyoung]
- DGIST Authors
- Jeon, Y[Jeon, Yoonjeong]; Ronnett, GV[Ronnett, Gabriele V.]; Kim, EK[Kim, Eun-Kyoung]
- Issue Date
- Biochemical and Biophysical Research Communications, 470(4), 818-823
- Article Type
- 4-(2-Amino-2-Deoxygalactopyranosyl)-3-O-Methylinositol; Animal; Animal Cell; Animal Experiment; Animals; Body Weight; C57Bl Mouse; Cell Line; Controlled Study; Dextro Chiro Inositol Glycan; Disaccharide; Disaccharides; Dose-Response; Dose-Response Relationship, Drug; Down-Regulation; Drug Effects; Eating; Food Intake; Forkhead Transcription Factor; Forkhead Transcription Factors; Foxo1 Protein, Mouse; Gene Expression Regulation; Glycan; Hypothalamus; Infant; Inositol Phosphate; Inositol Phosphate Glycan; Inositol Phosphates; INS-2; Insulin; Male; Metabolic Disorder; Metabolism; Mice; Mice, Inbred C57BL; Mouse; Nerve Cell; Neuropeptide; Neuropeptide Y; Neuropeptides; Non-Human; Obesity; Physiology; Polysaccharide; Polysaccharides; Priority Journal; Proopiomelanocortin; Protein Expression; Protein Kinase B; Proto-Oncogene Proteins C-AKT; Signal Transduction; Transcription Factor FKHR; Unclassified Drug; Upregulation
- 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. © 2016 Elsevier Inc. All rights reserved.
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