The nonalcoholic steatohepatitis is accompanied by Slc2a2, Pck1 and G6pc superexpression and increased glucose liver eflux.

Author(s)

Aline David Silva

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2016-06-10

Examining board members

Ubiratan Fabres Machado; Luciana Chagas Caperuto; William Tadeu Lara Festuccia; Eliane Beraldi Ribeiro; Telma Maria Tenorio Zorn

• Advisor: Ubiratan Fabres Machado

Abstract

The non-alcoholic steatohepatitis (NASH) has higher hepatic glucose efflux and hyperglycemia. We studied the role of hyperglycemia and glucose metabolism in liver of obese mice (MSG) with NASH treated with high fat diet (HFD) or phlorizin. In the liver MSG independently of HFD, we observed: 1) diagnosis of NASH; 2) increased TNFa, IL6 and Rela mRNAs; 3) increased Slc2a2, pCK1, G6pc mRNAs and their GLUT2, PEPCK and G6Pase proteins; 4) reduction of GCK mRNA and its protein GCK; 5) increased glycogen and glucose efflux; 6) insulin resistance, hyperinsulinaemia, hyperglycaemia; and 7) increased activity of transcription factors HNF4A, HNF3B, HNF1A and NFKB. The phlorizin: 1) normalized blood glucose; 2) attenuated NASH; and 3) reversed the changes related to carbohydrate metabolism and glucose efflux. The NASH increases the expression of the GLUT2 and gluconeogenic enzymes, promoting higher glucose efflux and hyperglycemia. These changes are reversed by glycemic fall, revealing hyperglycemia as pathogenetic factor. (AU)

• FAPESP's process: 11/09463-8 - TRANSCRIPTIONAL REGULATION OF SLC2A2 GENE IN LIVER OF NON-ALCOHOLIC STEATOHEPATITIS ANIMALS.
• Grantee: Aline David Silva
• Support Opportunities: Scholarships in Brazil - Doctorate