title: Chronic central leptin infusion differently modulates brain and liver insulin signaling.
abstract: Recent studies reported the impact of leptin on peripheral insulin sensitivity and glucose utilization. However, little is known concerning the effect of central leptin on hypothalamic and hepatic insulin efficiency. This study aimed to determine the consequence of chronic intra-cerebroventricular (ICV) leptin or murine leptin antagonist (MLA) infusion on hypothalamic and hepatic insulin signaling pathways, in rats. A 2-week central leptin infusion enhanced insulin-dependent Akt phosphorylation in the liver without changing PTP-1B protein expression, associated to insulin receptor (IR) upregulation and reduced IRS-1 phosphorylation on Ser302 residue. In the hypothalamus, a chronic ICV leptin infusion induced PTP-1B associated with a specific decrease in insulin-dependent Akt phosphorylation. In contrast, a chronic MLA infusion did not alter IR and PTP-1B expressions in hypothalamus and liver. Our results underline a brain leptin-dependent increase in hepatic insulin efficiency as mirrored by IR up-regulation, increased insulin-dependent Akt phosphorylation and reduced IRS-1 phosphorylation on Ser302 residue.
authors.affiliation: Neuroendocrinologie Moléculaire de la Prise Alimentaire, University of Paris-Sud, France.
authors.forename: Flavien
authors.initials: F
authors.lastname: Berthou
authors.forename: Claude
authors.initials: C
authors.lastname: Rouch
authors.forename: Arieh
authors.initials: A
authors.lastname: Gertler
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Gerozissis
authors.forename: Mohammed
authors.initials: M
authors.lastname: Taouis
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D007328:Insulin / Q000008:administration & dosage / Q000097:blood*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D020738:Leptin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D020738:Leptin; D012333:RNA, Messenger; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; C521086:murine leptin analog; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516610:Ptpn1 protein, rat