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Investigation of adiponectin and beta-adrenergic pathway mediating the anti-obesity effects of green tea polyphenols

Grant number: 16/12059-8
Support Opportunities:Regular Research Grants
Duration: March 01, 2017 - February 28, 2019
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Rosemari Otton
Grantee:Rosemari Otton
Host Institution: Pró-Reitoria de Pós-Graduação e Pesquisa. Universidade Cruzeiro do Sul (UNICSUL). São Paulo , SP, Brazil
Associated researchers:Alice Cristina Rodrigues ; Miriam Oliveira Ribeiro


Obesity is a risk factor for numerous diseases, including type 2 diabetes, hypertension, osteoporosis, cancer, neurodegenerative diseases, atherosclerosis and non-alcoholic fatty liver disease. This risk can be reduced considerably with weight loss due to increased physical activity associated with interventions that result in nutritional education, as the increase in consumption of diets rich in bioactive compounds with nutraceutical properties. The polyphenolic compounds including flavonoids from green tea, are nutraceuticals emerging as important health benefits due to its anti-inflammatory and anti-obesity effects, the lack of adverse effects, and reduced cost. In published studies and some still in progress of our research group we have shown that green tea promotes an increase in lipolytic activity and a reduction of lipogenic capacity of epididymal adipose tissue, associated with an increase in energy expenditure and induction beige phenotype in subcutaneous adipose tissue of animals fed a high fat diet. These changes in adipose tissue of obese animals treated with tea been accompanied by an increased release of adiponectin, improved insulin sensitivity and reduced systemic inflammation and hepatic steatosis. Among the effects attributed to the green tea polyphenols, is the increase in gene expression that characterize beige fatty tissue recently discovered and proposed as a potential target for the treatment of obesity. In addition, we found that green tea modulates some miRNAs in epididymal adipose tissue and liver of obese animals involved in inflammation processes, insulin resistance and lipid metabolism, as well as restore the levels of adiponectin, reduced by obesity. Therefore, our hypothesis is largely based on the effects of green tea in obese mice may arise from the adiponectin increase in plasma, with consequent increase of its action on target tissues, which in turn culminates in reducing fat deposits in improved insulin sensitivity and reduced systemic inflammation. We also hypothesized that the effects of green tea may be mediated in part by the increased adrenergic stimulation on adipose tissue and liver. To better understand these mechanisms the general objective of this study was to investigate the involvement of adiponectin and adrenergic stimulation on the thermogenic effects and insulin resistance in AdipoKO and ²3KO mice exposed to a high fat diet (HFD) and treated with green tea. Based on our preliminary results, we believe that AdipoKO and ²3KO mice fed a HFD and treated with green tea not show a significant reduction in body weight, in fat depots, in systemic inflammation and insulin resistance, and did not significantly increase beige cells and the activity of the brown adipose, because these animals are refractory to the effects of green tea, since the actions of green tea, in our case, are mediated adiponectin and / or increased adrenergic stimulation. To achieve these goals we intend to compose a multicentric and multidisciplinary team to assess the AdipoKO mice and obese ²3KO as will the intervention treatment with green tea. With this team and these animal models we will be able to define the effective contribution of adiponectin and the sympathetic nervous system in the anti-obesity and anti-inflammatory actions of green tea. Besides this approach in vivo, we will perform in vitro analysis of the autonomous capacity of polyphenolic compounds in green tea to induce beige phenotype, by treating white preadipocytes 3-T3F442A cell line during the differentiation process with isolated polyphenols, combined or as extract. In addition, we will perform an induction of steatosis in vitro in HepG2 cells and assess the effects of polyphenols in this process. With this project we aim to include specialists in different areas and different research centres in order to reveal a new mechanism for regulation of green tea in adipose and liver tissue, which could serve as a pharmacological treatment for hea (AU)

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Scientific publications
(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)
FERREIRA, LETICIA TORRES; BATISTA DE SOUSA FILHO, CELSO PEREIRA; MARINOVIC, MARCELO PARADISO; RODRIGUES, ALICE CRISTINA; OTTON, ROSEMARI. Green tea polyphenols positively impact hepatic metabolism of adiponectin-knockout lean mice. Journal of Functional Foods, v. 64, . (16/12059-8, 15/24789-8, 15/21785-1)
BOLIN, ANAYSA PAOLA; SOUSA-FILHO, CELSO PEREIRA BATISTA; MARINOVIC, MARCELO PARADISO; RODRIGUES, ALICE CRISTINA; OTTON, ROSEMARI. Polyphenol-rich green tea extract induces thermogenesis in mice by a mechanism dependent on adiponectin signaling. JOURNAL OF NUTRITIONAL BIOCHEMISTRY, v. 78, . (17/10531-4, 11/19216-8, 16/12059-8, 12/20415-8)
BATISTA SOUSA-FILHO, CELSO PEREIRA; FERNANDES FARIA, HECTOR ORELIANA; ESPOSITO, JULIANA CARVALHO; MELO, ALESSANDRA; RIBEIRO, MIRIAM OLIVEIRA; OTTON, ROSEMARI. Green tea improves the metabolism of peripheral tissues in beta 3-adrenergic receptor-knockout mice. PHARMACOLOGICAL RESEARCH, v. 159, . (16/12059-8)

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