Evaluation of TrkB role on non-alcoholic fatty liver disease (NAFLD) in mice

• Grant number: 15/02052-3
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2015
• End date: January 31, 2018
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Marcelo Augusto Christoffolete
• Grantee: Marcelo Augusto Christoffolete
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Non-alcoholic Fatty Liver Disease (NAFLD)affects baout 20% of world population and is being considered the hepatic manifestation of metabolic syndrome. It is chacterized by fat accumulation (steatose) and may evolve to non-alcoholic steato-hepatitis (NAS), the more severe form of the disease, which can progress to cirrosis or hepatocarcinoma.Brain derived neurotropic factor (BDNF)has its signaling pathway trough its receptor, Tyrosine Kinase Receptor, isoform b (TrkB), mediating neuron survival, differentiation and plasticity, and its role in brain is essential for appetite control.In liver, BDNF/TrkB pathway has a repressor effect on oxidation/exportation of fatty acids, promoting steatosis. Hepatic-specific deletion of this pathway has a protective effect against deleterious effects of high fat diet over triglycerides and glucose metabolism in liver.In our previous studies, we found TrkB expression to be about 20x higher in liver of FVB/N animals comparing to C57Bl6/J and when challenged with high fat diet FVB/N mice develop pronounced steatosis when compared to C57Bl6/J.Considering the pronounced effect of TrkB in energy balance and crescent interest using TrkB agonists as anti-obesity drugs, troughout its anorexigenic feature in central nervous system, it is indispensable to evaluate its role in development of NAFLD in liver. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

NASCIMENTO-SALES, MICHELLE; FREDO-DA-COSTA, IZABELLE; BORGES MENDES, ADRIANE C. B.; MELO, SUZANE; RAVACHE, THAIS T.; GOMEZ, THIAGO G. B.; GAISLER-SILVA, FERNANDA; RIBEIRO, MIRIAM O.; SANTOS, JR., ARNALDO R.; CARNEIRO-RAMOS, MARCELA S.; et al. Is the FVB/N mouse strain truly resistant to diet-induced obesity?. PHYSIOLOGICAL REPORTS, v. 5, n. 9, MAY 2017. (08/10700-1, 15/02052-3)

GAISLER-SILVA, FERNANDA; CRUZ JUNHO, CAROLINA VICTORIA; FREDO-DA-COSTA, IZABELLE; CHRISTOFFOLETE, MARCELO AUGUSTO; CARNEIRO-RAMOS, MARCELA SORELLI. Diet-induced Obesity Differentially Modulates Cardiac Inflammatory Status in the C57 and FVB Mouse Strains. CURRENT MOLECULAR MEDICINE, v. 22, n. 4, p. 9-pg., 2022-01-01. (15/02052-3, 15/19107-5, 18/07811-8, 19/11077-0)