Low Birth Weight Intensifies Changes in Markers of Hepatocarcinogenesis Induced by Fructose Consumption in Rats

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Almeida, Lorena de Souza ; Teixeira, Caio Jordao ; Campos, Carolina Vieira ; Casaloti, Lais Guadalupe ; Sodre, Frhancielly Shirley ; Capetini, Vinicius Cooper ; Amaral, Andressa Godoy ; Payolla, Tanyara Baliani ; Pantaleao, Lucas Carminatti ; Anhe, Gabriel Forato ; Bordin, Silvana

• Tipo de documento: Artigo Científico
• Fonte: METABOLITES; v. 12, n. 10, p. 15-pg., 2022-10-01.

Resumo

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. (AU)

• Processo FAPESP: 13/07607-8 - CMPO - Centro Multidisciplinar de Pesquisa em Obesidade e Doenças Associadas
• Beneficiário: Licio Augusto Velloso
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 20/13940-5 - Impactos da história transitória de obesidade em diferentes momentos da vida sobre a inflamação pulmonar alérgica
• Beneficiário: Gabriel Forato Anhê
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 19/03196-0 - Mecanismos moleculares envolvidos na inflexibilidade metabólica de ratos submetidos à programação fetal por excesso de glicocorticoides
• Beneficiário: Silvana Auxiliadora Bordin da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 20/06397-3 - Investigação da senescência celular em roedores submetidos à Obesidade
• Beneficiário: Caio Jordão Teixeira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado