Molecular control of HIF1-A expression and response to insulin mediated by PPAR in muscle cells

• Grant number: 17/25168-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2018
• End date: February 28, 2019
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Leonardo dos Reis Silveira
• Grantee: Rafaela Mariano da Silva Araujo
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 16/23008-5 - Identification and functional characterization of protein bound to NCoR1 complex and associated with molecular control of mitochondrial biogenesis process, AP.TEM

Abstract

The nuclear receptor PPAR² is an important transcriptional regulator of the mitochondrial biogenesis process in peripheral tissue cells including skeletal muscle. Recent researches has demonstrated that the expression of hypoxia-inducible transcription factor (HIF-1a) is increased in tissue / muscle cells with high mitochondrial capacity induced by exercise or overexpression of PGC-1a (1,2). Preliminary experiments from our laboratory showed that treatment of muscle cells with the PPAR (GW) or AMPK inducer (AICAR) increased expression of the HIF-1a protein suggesting that PPAR may be an important regulator of HIF-1a expression. We hypothesized that PPAR regulates the expression of HIF-1a in muscle tissue cells. If this is confirmed, the PPAR² / HIF1a axis may constitute an important therapeutic target as against the installation of pathologies related to mitochondrial dysfunction in muscle tissue, including insulin resistance.