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| Author(s): |
Tanyara Baliani Payolla
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2019-06-17 |
| Examining board members: |
Silvana Auxiliadora Bordin da Silva;
Luciana Chagas Caperuto;
Carolina Demarchi Munhoz;
Thomas Prates Ong
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| Advisor: | Silvana Auxiliadora Bordin da Silva |
| Abstract | |
Phenotypic programming caused by distinct environmental changes and associated with high fructose consumption in adulthood could contribute to the worsening of metabolic disorders. To evaluate whether prenatal exposure to Dexamethasone (DEX) modulates the effects of fructose consumption on hepatic metabolism, we investigated male offspring born to Wistar rats treated with or without DEX (0.2 mg / kg body weight / day) at 3rd gestational period. The offspring of control (untreated) and DEX treated mothers were maintained without fructose (CTL and DEX) or supplemented with 10% fructose solution for 8 weeks (fructose and DEX+fructose). Both the fructose and DEX+fructose groups showed similar fructose consumption, glucose intolerance and increased maximal activity of the glycolytic enzyme PFK. Only DEX+fructose presented increase in hepatic triglycerides and accumulation of intrahepatic lipids. In addition, the DEX + fructose group did not show increased expression of sec22, mttp and apoB genes involved in the synthesis, assembly and secretion of VLDL; in parallel, we observed a decrease in TG concentration in 6 hours after injection of Tyloxapol, compared to DEX and fructose. In addition, there was a decrease in BECLIN1 expression, HSP90 gene expression, and alteration of HCC-related molecular markers such as TP53, P21 and TIGAR, and increased expression of afp and hsp70 mRNA. Taken together, our data indicate that exposure to DEX in utero leads to a unique metabolic response to high fructose intake in adult life. Increased gluconeogenesis and glucose intolerance, reduction in VLDL production and secretion, and loss of autophagic flow stimulate the accumulation of lipid droplets in the liver, that may favor the development of HCC in response to high fructose intake. (AU) | |
| FAPESP's process: | 15/25597-5 - Hepatic microRNA expression profile in Goto-Kakizaki rats and Wistar rats subjected to metabolic programming by prenatal exposure to glucocorticoid excess |
| Grantee: | Tanyara Baliani Payolla |
| Support Opportunities: | Scholarships in Brazil - Doctorate |