The over-expression of miR-200a in the hypothalamus of ob/ob mice is linked to leptin and insulin signaling impairment.

Delphine Crépin (1, 2) , Yacir Benomar (1, 2) , Laure Riffault (1, 2) , Hamza Amine (1, 2) , Arieh Gertler (3) , Mohammed Taouis (1, 2)

1 NeuroPSI - Institut des Neurosciences Paris-Saclay
2 CNPS - Centre de Neurosciences Paris-Sud
3 Institute of Biochemistry Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment

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.

Domaines: Neurobiologie; Psychologie et comportements; Sciences cognitives

Delphine Crépin, Yacir Benomar, Laure Riffault, Hamza Amine, Arieh Gertler, et al.. The over-expression of miR-200a in the hypothalamus of ob/ob mice is linked to leptin and insulin signaling impairment.. Molecular and Cellular Endocrinology, 2014, 384 (1-2), pp.1-11. ⟨10.1016/j.mce.2013.12.016⟩. ⟨hal-01179301⟩