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LIVER REGENERATION CAPABILITY ASSESSMENT AND ITS RELATIONSHIP WITH LIN28/LET-7 PATHWAY IN THE OFFSPRING OF MICE SUBMITTED TO HIGH-FAT DIET DURING GESTATION AND LACTATION

Grant number: 19/03351-5
Support type:Regular Research Grants
Duration: July 01, 2019 - June 30, 2021
Field of knowledge:Health Sciences - Nutrition - Nutrition Biochemistry
Principal researcher:Adriana Souza Torsoni
Grantee:Adriana Souza Torsoni
Home Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
Assoc. researchers:Marcio Alberto Torsoni

Abstract

In recent decades, obesity and the metabolic syndrome have become increasingly prevalent in the world population. Recently the consequences of lipid overload during critical periods of development on the metabolism of offspring, through epigenetic changes, have been evidenced contributing to the development of obesity and its complications, such as hepatic steatosis. Among the epigenetic mechanisms, the modulation of microRNAs has been highlighted by its direct action on target genes, through post-transcriptional regulation. The let-7 microRNA family was one of the first described and is known for its interaction with proteins involved in tissue development, proliferation and repair processes, among them LIN28. For regeneration to be favored, it is necessary that LIN28 has its expression increased, with consequent negative modulation of let-7. Recent data from our laboratory showed that high-fat diet consumption leads to increased hepatic expression of let-7. The literature shows that hepatic steatosis can be a detrimental factor for cell regeneration processes, and that the offspring of obese dams are susceptible to the development of non-alcoholic fatty liver disease (NAFLD), which could lead to significant impairment in the process of tissue regeneration. This fact is even more worrying when considering the possibility of progression of NAFLD to cirrhosis or hepatocellular carcinoma, which require some type of organ resection. Thus, the present study aims to evaluate the hepatic regeneration capacity in both obese and offspring of obese dams after mechanical injury induced by partial hepatectomy (2/3PHx), to understand the role of the let-7/LIN28 axis in this process and its implications for the individual survival after surgery. (AU)

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