title: D-chiro-inositol glycan reduces food intake by regulating hypothalamic neuropeptide expression via AKT-FoxO1 pathway.
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 Mn(2+) 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.
authors.affiliation: Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science & Technology, Daegu, Republic of Korea.
authors.forename: Yoonjeong
authors.initials: Y
authors.lastname: Jeon
authors.affiliation: Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Aja
authors.affiliation: Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science & Technology, Daegu, Republic of Korea; Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Gabriele V
authors.initials: GV
authors.lastname: Ronnett
authors.affiliation: Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science & Technology, Daegu, Republic of Korea; Neurometabolomics Research Center, Daegu Gyeongbuk Institute of Science & Technology, Daegu, Republic of Korea. Electronic address: ekkim@dgist.ac.kr.
authors.forename: Eun-Kyoung
authors.initials: EK
authors.lastname: Kim
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D004187:Disaccharides / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D007295:Inositol Phosphates / Q000008:administration & dosage; D007328:Insulin / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009479:Neuropeptides / Q000378:metabolism*; D011134:Polysaccharides / Q000008:administration & dosage; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: C476439:4-(2-amino-2-deoxygalactopyranosyl)-3-O-methylinositol; D004187:Disaccharides; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D007295:Inositol Phosphates; D007328:Insulin; D009479:Neuropeptides; D011134:Polysaccharides; C028039:inositol phosphate glycan; D051057:Proto-Oncogene Proteins c-akt
keywords: Food intake; INS-2; Neuropeptide Y; Proopiomelanocortin