Role of miR-200a in regulating the insulin signalling in the hypothalamus

Abstract

Leptin and Insulin mediated signalling have been known to play a significant role in energy utilization and body weight. Obese mice with leptin mutations were known to have several impairments but the contribution of micro RNA to the manifestation of these impairments in the Ob/ Ob mice (lacking functional leptin) were not explored in detail. miRNA play an important role in regulating obesity was indicated by the obese phenotype of the mice lacking Dicer in the PMOC neuron [1]. Leptin is an essential neurotrophic factor in early development and also reduced Leptin during early development results in obesity, thus it can be hypothesized that some of the effects of the leptin deprivation could be mediated by miRNAs. Recently Crepin and co-workers have studied differential expression of micro RNAs in the hypothalamus of the Ob/Ob mice compared to control mice [2]. In the initial screen using Taqman Low Density assay (TLDA) array they identified eleven miRNA’s that are differentially expressed and three of these miRNA (miR-200a, miR-200b and miR-429) were further analysed by quantitative PCR to confirm their over expression in Ob/Ob mice. Further, the authors have demonstrated that leptin treatment in ob/ob mice reduces the expression of miR-200a, miR-200b and miR-429 when compared to the vehicle control. miR200a was also shown to be upregulated in the db/db mice (lacking functional leptin receptors). IRS2 and Leptin receptor (ObRb) mRNA were identified as functional target of miR-200a. Using luciferase reporter assay they, have demonstrated that miR-200a targets the 3’UTR region of insulin receptor substrate 2 (IRS2) and leptin receptor (ObRb) in CHO cells. Interestingly, Commentary