Low Birth Weight Intensifies Changes in Markers of Hepatocarcinogenesis Induced by Fructose Consumption in Rats
Lorena de Souza Almeida,
Caio Jordão Teixeira,
Carolina Vieira Campos,
Laís Guadalupe Casaloti,
Frhancielly Shirley Sodré,
Vinícius Cooper Capetini,
Andressa Godoy Amaral,
Tanyara Baliani Payolla,
Lucas Carminatti Pantaleão,
Gabriel Forato Anhê,
Silvana Bordin
Affiliations
Lorena de Souza Almeida
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, 105 Alexander Flemming St., Campinas 13083-881, SP, Brazil
Caio Jordão Teixeira
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, 1524 Prof. Lineu Prestes Ave., ICB 1, Sao Paulo 05508-000, SP, Brazil
Carolina Vieira Campos
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, 105 Alexander Flemming St., Campinas 13083-881, SP, Brazil
Laís Guadalupe Casaloti
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, 105 Alexander Flemming St., Campinas 13083-881, SP, Brazil
Frhancielly Shirley Sodré
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, 1524 Prof. Lineu Prestes Ave., ICB 1, Sao Paulo 05508-000, SP, Brazil
Vinícius Cooper Capetini
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, 105 Alexander Flemming St., Campinas 13083-881, SP, Brazil
Andressa Godoy Amaral
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, 1524 Prof. Lineu Prestes Ave., ICB 1, Sao Paulo 05508-000, SP, Brazil
Tanyara Baliani Payolla
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, 1524 Prof. Lineu Prestes Ave., ICB 1, Sao Paulo 05508-000, SP, Brazil
Lucas Carminatti Pantaleão
Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge CB2 0QQ, UK
Gabriel Forato Anhê
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, 105 Alexander Flemming St., Campinas 13083-881, SP, Brazil
Silvana Bordin
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, 1524 Prof. Lineu Prestes Ave., ICB 1, Sao Paulo 05508-000, SP, Brazil
Intrauterine growth restriction (IUGR) due to fetal exposure to glucocorticoid excess results in metabolic inflexibility and hepatic steatosis upon nutritional stress during adulthood. We previously demonstrated that rats born to dexamethasone (DEX)-treated mothers developed hepatic steatosis when exposed to 10% fructose solution during adult life. Persistent triacylglyceride (TAG) accumulation in the liver, in turn, is a feature of non-alcoholic fatty liver disease (NAFLD), which serves as a risk factor for non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). In the present study, we demonstrate that the combination of IUGR and fructose treatment during adulthood also results in increased hepatic myeloperoxidase (MPO) activity, AKT phosphorylation and serum aspartate transaminase. Growth-restricted rats also presented reduced hepatic TRIB3 and GADD45a after fructose treatment. Other markers of cell proliferation, such as Cyclin D, PCNA, Hgf and Hspa4/Hsp70 expression and the number of Ki-67 positive cells, were all increased in the liver of growth- restricted rats treated with fructose. On the other hand, the combination of IUGR and fructose treatment during adult life reduced the levels of IGF-1. In conclusion, our data indicate that after exposure to fructose, adult rats subjected to dexamethasone-induced IUGR display exacerbated molecular changes in markers of NASH and HCC.
