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

• Document type: Journal article
• Source: METABOLITES; v. 12, n. 10, p. 15-pg., 2022-10-01.

Abstract

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)

• FAPESP's process: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center
• Grantee: Licio Augusto Velloso
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 20/13940-5 - Transitory history of obesity during different moments of life and its impact on allergy airway disease
• Grantee: Gabriel Forato Anhê
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/03196-0 - Molecular mechanisms involved in the metabolic inflexibility of rats submitted to metabolic programming induced by prenatal excess of glucocorticoids
• Grantee: Silvana Auxiliadora Bordin da Silva
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/06397-3 - Study of cellular senescence in rodents subjected to Obesity
• Grantee: Caio Jordão Teixeira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral