MicroRNAs analysis in the hypothalamus of trained and high fat diet-fed C57BL/6 mice

• Grant number: 16/03047-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2016
• End date: April 30, 2017
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Helena Cristina de Lima Barbosa
• Grantee: Jéssica de Assis Sofiatti
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID

Abstract

The control of energy balance occurs in the central nervous system (CNS) through neuroendocrine connections, where leptin and insulin are important signaling hormones in specialized neurons in the hypothalamus. These hormones primarily activate the JAK-STAT and IRS-AKT signaling pathways for neuronal activities. Inflammatory processes impair these signaling pathways in individuals resistant to leptin and insulin, and reversal of the resistance implies in a better action of these hormones. A response to hypothalamic inflammation that contributes to the resistance to leptin and insulin are mediated by PTP1B and SOCS3 proteins which are inhibitors of signaling of these hormones. The miRs control the expression and activity of the various components involved in hypothalamic sensitivity and is likely to play the same regulatory role on proteins involved in the hypothalamic hormone sensitivity. Decreased circulating leptin associated to increased leptin sensitivity is observed in trained animal models, improving the inflammatory effects of obesity. Whereas miRs represent a new perspective on therapy to control metabolic disorders, it is important to elucidate the mechanisms of action of miRs and its possible hypothalamic targets in response to exercise in an obesity model. Thus, this project aims to study the effect of HFD and physical exercise on the leptin signaling pathway through the phosphorylation of JAK2 and STAT3 in the hypothalamus; gene and protein expression of hypothalamic SOCS3 and PTP1B proteins, the expression of miR9, Let7c, miR7a and miR200a miR in the hypothalamus, as well as to correlate the expression of miRs with the improved hypothalamic sensitivity and phosphorylation of JAK2 and STAT3 in our animal models.