title: The over-expression of miR-200a in the hypothalamus of ob/ob mice is linked to leptin and insulin signaling impairment.
abstract: Early in life, leptin plays a crucial role in hypothalamic neural organization. Leptin, most likely, controls neural gene expression conferring then specific phenotype regarding energy homeostasis. MicroRNAs are new regulators for several physiological functions, including the regulation of metabolism. However, the impact of leptin on hypothalamic microRNA patterns remains unknown. Here, we demonstrate that miR-200a, miR-200b and miR-429 are up-regulated in the hypothalamus of genetically obese and leptin deficient ob/ob mice. Leptin treatment down-regulates these miRNAs in ob/ob hypothalamus. The hypothalamic silencing of miR-200a increased the expression level of leptin receptor and insulin receptor substrate 2, reduced body weight gain, and restored liver insulin responsiveness. In addition, the overexpression of pre-miR-200a in a human neuroblastoma cell line impaired insulin and leptin signaling. These findings link the alteration of leptin and insulin signaling to the up-regulation of hypothalamic miR-200a which could be a new target for treatment of obesity.
authors.affiliation: CNRS, Center of Neurosciences Paris-Sud, UMR 8195, Orsay cedex F-91405, France; University Paris-Sud, UMR 8195, Orsay cedex F-91405, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Crépin
authors.affiliation: CNRS, Center of Neurosciences Paris-Sud, UMR 8195, Orsay cedex F-91405, France; University Paris-Sud, UMR 8195, Orsay cedex F-91405, France.
authors.forename: Yacir
authors.initials: Y
authors.lastname: Benomar
authors.affiliation: CNRS, Center of Neurosciences Paris-Sud, UMR 8195, Orsay cedex F-91405, France; University Paris-Sud, UMR 8195, Orsay cedex F-91405, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Riffault
authors.affiliation: CNRS, Center of Neurosciences Paris-Sud, UMR 8195, Orsay cedex F-91405, France; University Paris-Sud, UMR 8195, Orsay cedex F-91405, France.
authors.forename: Hamza
authors.initials: H
authors.lastname: Amine
authors.affiliation: The Institute of Biochemistry, Food Science, and Nutrition, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, PO Box 12, 76100 Rehovot, Israel.
authors.forename: Arieh
authors.initials: A
authors.lastname: Gertler
authors.affiliation: CNRS, Center of Neurosciences Paris-Sud, UMR 8195, Orsay cedex F-91405, France; University Paris-Sud, UMR 8195, Orsay cedex F-91405, France. Electronic address: mohammed.taouis@u-psud.fr.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Taouis
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005247:Feeding Behavior; D005786:Gene Expression Regulation; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism* / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000172:deficiency / Q000235:genetics*; D008099:Liver / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009765:Obesity / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D054411:Receptors, Leptin / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015430:Weight Gain
chemical_list: D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526298:Irs2 protein, mouse; D020738:Leptin; C582202:MIRN429 microRNA, mouse; D035683:MicroRNAs; C543719:Mirn200 microRNA, mouse; D054411:Receptors, Leptin
keywords: Insulin-resistance; Liver; MicroRNAs; Neurons; Obesity; Signaling