The role of microRNA in body weight maintenance

• Applicant: Professor Dr. Nikolaus Rajewsky
• Subject Area: Pediatric and Adolescent Medicine ; Endocrinology, Diabetology, Metabolism
• Term: from 2009 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 101434729

Based on previous research on the role of genes within the leptin-melanocortin pathway in human weight regulation and the comprehensive expression profiling of microRNA targeted genes as well as the quantification of serum microRNA a thorough study of the physiological roles of microRNA in the regulatory circuits of weight regulation seem to be timely due. Loss of function mutations within the leptin-melanocortin pathway have uncovered the dosage sensitive genetic regulation of human body weight. Only few individuals are affected by those monogenetic defects. However because most obese patients are leptin resistant other molecular mechanisms leading to a dysregulation of leptin responsive genes are likely to be expected during the course of obesity pathogenesis. MicroRNAs regulate gene function by a target gene specific suppression of protein synthesis. Alterations in the microRNA related gene function of the hypothalamic neuroendocrine circuits represent one possible mechanism involved in the molecular pathogenesis of obesity. Moreover, a variey of microRNAs have been identified in serum as stable, and therefore potentially physiological relevant molecules, leading to the hypothesis of an additional „endocrine“ level of regulation based on cell to cell signalling by microRNAs. Therefore, studies in mice and human will be performed –in association with the z-project and project 8- to unravel a potential regulatory role of microRNAs for body weight regulation with a special emphasis on genes involved in hypothalamic weight regulation and on a new endocrine function of serum microRNAs.

• DFG Programme: Clinical Research Units
• Subproject of: KFO 218: Hormonal Regulation of Body Weight Maintenance
• International Connection: USA
• Participating Persons: Professorin Dr. Heike Biebermann; Professor Dr. Heiko Krude; Professor Dr. Thomas Tuschl