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Evaluation of non-alcoholic fatty liver disease (NAFLD) susceptibility dependent of truncated neurotrophic tyrosine receptor kinase 2 (NTRK2.T1) in liver of C57BL/6J mice conditionally over-expressing and FVB/N conditionally supressing this receptor

Grant number: 18/07811-8
Support type:Regular Research Grants
Duration: August 01, 2018 - January 31, 2021
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Marcelo Augusto Christoffolete
Grantee:Marcelo Augusto Christoffolete
Home Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Non-Alcahoolic Fatty Liver Disease prevalence is around one-fourth worldwide, being considered the hepatic component of metabolic syndrome. It is characterized by fat accumulation in liver (steatosis) and can develop to non-alcoholic steato-hepatitis (NASH). Brain derived neurotrophic factor (BDNF) signaling cascade requires neurotrophic receptor tyrosine kinase (NTRK2), mediating neuron survival, differentiation and plasticity, and in brain, this pathway is essential for appetite control.In liver, this signaling cascade represses oxidation/exportation of fat acids, leading to steatosis.In previous work, our group identified a 20x higher expression of NTRK2 in liver of FVB/N mouse strain, compared to C57Bl/6J strain. When challenged with high fat diet, FVB/N animals presented severe steatosis compared to C57Bl/6J.We also identified that truncated version of NTRK2 receptor (NTRK2.T1) is predomanately expressed in FVB/N hepatocytes.Considering the pronounced effect of BDNF/NTRK2 pathway in energy balance and the crescent interest in using agonists to treat obesity, via anorexigenic effects in central nervous system, it is important to evaluate this pathway role in development of NAFLD. Despite our previous results show a key role for NTRK2.T1 in this process in vitro, animals models manipulating NTRK2.T1 expression in liver are of great value to further understand NAFLD development. (AU)