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

Title
D-chiro-inositol glycan reduces food intake by regulating hypothalamic neuropeptide expression via AKT-FoxO1 pathway
Authors
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
2016-02-19
Citation
Biochemical and Biophysical Research Communications, 470(4), 818-823
Type
Article
Article Type
Article
Keywords
4-(2-Amino-2-Deoxygalactopyranosyl)-3-O-MethylinositolAnimalAnimal CellAnimal ExperimentAnimalsBody WeightC57Bl MouseCell LineControlled StudyDextro Chiro Inositol GlycanDisaccharideDisaccharidesDose-ResponseDose-Response Relationship, DrugDown-RegulationDrug EffectsEatingFood IntakeForkhead Transcription FactorForkhead Transcription FactorsFoxo1 Protein, MouseGene Expression RegulationGlycanHypothalamusInfantInositol PhosphateInositol Phosphate GlycanInositol PhosphatesINS-2InsulinMaleMetabolic DisorderMetabolismMiceMice, Inbred C57BLMouseNerve CellNeuropeptideNeuropeptide YNeuropeptidesNon-HumanObesityPhysiologyPolysaccharidePolysaccharidesPriority JournalProopiomelanocortinProtein ExpressionProtein Kinase BProto-Oncogene Proteins C-AKTSignal TransductionTranscription Factor FKHRUnclassified DrugUpregulation
ISSN
0006-291X
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. © 2016 Elsevier Inc. All rights reserved.
URI
http://hdl.handle.net/20.500.11750/2721
DOI
10.1016/j.bbrc.2016.01.115
Publisher
Elsevier
Related Researcher
Files:
There are no files associated with this item.
Collection:
Brain and Cognitive SciencesETC1. Journal Articles
Brain and Cognitive SciencesETC1. Journal Articles


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