Modulation of endoplasmic reticulum stress in adipocytes and leukocytes of mice induced to obesity and chronically treated with green tea extract (Camellia sinensis)

• Grant number: 12/20415-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): April 01, 2013
• Effective date (End): November 16, 2017
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Rosemari Otton
• Grantee: Anaysa Paola Bolin
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 16/10114-1 - THE ROLE OF ENDOPLASMIC RETICULUM STRESS IN MICE WITH D2 POLYMORPHISM INDUCED TO OBESITY, BE.EP.DR

Abstract

Obesity is currently one of the most serious public health problems around the world. One of the most important discoveries made recently in obesity research has been the role of chronic inflammation that occurs in obese patients. It is important to understand how excess body fat may disrupt metabolic functions and how these disorders comprise immune responses. Disturbances seen in obesity are able to cause stress in the endoplasmic reticulum (ER), being this cell organelle responsible for folding and maturation of proteins. During the stress the ER is able to adapt and if the stress persists the cell can lead to death. Tea made from the processed leaves of Camellia sinensis is consumed in different parts of the world as green tea, black tea or oolong tea. Catechins, the main polyphenolic compounds in green tea, exert different effects on human heath through multiple mechanisms, including antioxidant, anti-hypertensive, anti-inflammatory, anti-proliferative, anti-thrombogenic, antimutagenic, antidiabetic and lipid lowering effects. This study aims to evaluate systematically the effects of chronic supplementation of green tea extract on reticulum stress indicators related to obesity in mice induced to obesity by cafeteria diet. It will be evaluated reticulum stress in adipose tissue, adipocytes, and immune cells such as lymphocytes and neutrophils. Besides the experimental design in vitro experiments will be performed in order to evaluate the actions of the main catechin present in green tea, EGCG, on the reticulum stress in lymphocytes and neutrophils from human peripheral blood of healthy individuals. For this we will evaluate: (1) UPR pathway proteins through gene expression (mRNA expression by RT-PCR) of GADD34, CHOP, GRP78/BIP, GRP9, XBP1, and ATF4 and ATF6 protein expression and level of phosphorylation of eIF2a , Ire1 and PERK, (2) inflammatory process by assessing the gene expression of TNF-alfa, IL6, IL1b, IFN-y and MCP1 and protein expression and phosphorylation level of the proteins NFkB, MyD88, TLR4, JNK, p38 MAPK, ERK1 / 2 and Akt, (3) insulin resistance by expression and phosphorylation of JNK, IR, IRS1, Akt, PI3K and GLUT4 and (4) the involvement of ROS production. This study may contribute to understanding the involvement of the reticulum stress in obesity and specific action of green tea on these cells. Moreover, in the future this functional food may also be indicated as an adjunct in the treatment of complications of obesity. (AU)

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)

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, APR 2020. (17/10531-4, 11/19216-8, 16/12059-8, 12/20415-8)

BOLIN, ANAYSA PAOLA; BATISTA SOUSA-FILHO, CELSO PEREIRA; NASCIMENTO DOS SANTOS, GUSTAVO TOLENTINO; FERREIRA, LETICIA TORRES; MARTINS DE ANDRADE, PAULA BRESCIANI; MIGLIORINI FIGUEIRA, ANA CAROLINA; HELENO BATISTA, FERNANDA APARECIDA; OTTON, ROSEMARI. Adipogenic commitment induced by green tea polyphenols remodel adipocytes to a thermogenic phenotype. JOURNAL OF NUTRITIONAL BIOCHEMISTRY, v. 83, SEP 2020. (13/22293-0, 15/07024-8, 11/19216-8, 12/20415-8)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

BOLIN, Anaysa Paola. Investigation of the thermogenic and metabolic potential of the Camellia sinensis plant in obese mice - systemic repercussion of the beige phenotype.. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.