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Role of adrenergic receptor beta1 in non alcoolic fat liver disease


Obesity and metabolic syndrome results in a set of risk factors for developing cardiovascular disease and Non-Alcoholic Liver Disease (NAFLD). If left untreated, NAFLD can progress to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular carcinoma. Our working hypothesis considers the role of the ²1 adrenergic receptor in the development of obesity-induced NAFLD and its reversal by treatment with the selective agonist of thyroid hormone that binds preferentially to the T3 receptor (TR) of type ² (TR²) the major TR isoform present in the liver. Our hypothesis is based on two fundamental points: (i) our preliminary findings that knockout mice of the ²1 adrenergic receptor (²1KO) with diet-induced obesity have severe liver steatosis and fibrosis, much more serious than the control animals, and (ii) published studies showing that treatment with T3 can reverse fatty liver. Thus, our hypothesis will be tested in animals with ²1KO fed high-fat diet (40%) (HFD) and / or treated with T3 or GC-24, a super-selective agonist of TR². Our methodological approach will involve the analysis of physiological, biochemical and molecular techniques, including body weight, food intake, glucose tolerance tests and insulin and measurement of plasma lipids and inflammatory factors. Immediately after the death of animals, liver samples will be processed for analysis of hepatic enzymes involved in lipid metabolism Western blot. The analysis of these different parameters will hepl to understand the mechanisms involved in the development of NASH, as well as the interaction between the SNS and the thyroid hormone on hepatic metabolism of fat. (AU)

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(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FERNANDES, GUSTAVO W.; BOCCO, BARBARA M. L. C.; FONSECA, TATIANA L.; MCANINCH, ELIZABETH A.; JO, SUNGRO; LARTEY, LATTOYA J.; O-SULLIVAN, INSUG; UNTERMAN, TERRY G.; PREITE, NAILLIW Z.; VOIGT, ROBIN M.; et al. The Foxo1-Inducible Transcriptional Repressor Zfp125 Causes Hepatic Steatosis and Hypercholesterolemia. CELL REPORTS, v. 22, n. 2, p. 523-534, . (11/21847-6)

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