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Evaluation of genotoxicity associated to experimental obesity

Grant number: 18/06338-7
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2018
Effective date (End): June 30, 2019
Field of knowledge:Biological Sciences - Immunology - Immunogenetics
Principal Investigator:Niels Olsen Saraiva Câmara
Grantee:Nathalia Hiromi Ishida Assunção
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:17/05264-7 - Cell metabolism, microbiota and immune system: new paradigms in renal diseases physiopathology, AP.TEM


The obesity is a multifaceted disease and increases a person's risk of developing several disorders, including the cancer. Although both obesity-related inflammation and oxidative stress have been indicated as the main causes of tumor development, the underlying mechanisms associating obesity and cancer are still poorly understood. Since the DNA damage is an essential feature in cancer development and the obesity-related inflammatory responses produce high levels of reactive oxygen species, it is fair to assume that genotoxicity is a putative link between both infirmities. Therefore, the aim of this study is to evaluate the role of diet-induced obesity in DNA lesion and repair as well as the effect of the absence of DNA repair system on the obesity development. Our hypothesis is that local and/or systemic inflammation induced by obesity can cause DNA damage and impair the mechanisms of DNA repair in one or more cell types and thus contribute to the development/progression of tumors. To test this, wild type mice will be subjected to diet-induced obesity and their white adipose tissues (subcutaneous, abdominal and epididimal), brown adipose tissue, intestine, liver and lungs will be collected and evaluated for DNA damage idetification (³-H2AX detection). In addition, the expression of DNA repair-related genes (Xeroderma pigmentosum groups A - XPA - and C - XPC detection) and the gene expression or protein activity of antioxidant enzymes (superoxide dismutase, glutathione oxidase, catalase) will be also assessed. XPA- and XPC-deficient mice will be also induced to obesity to evaluate the impact of DNA repair absence in the clinical course of obesity (weight gain, glucose tolerance test, insulin tolerance test, metabolic assessment). Furthermore, it's known that both XPA- and XPC-deficient mice have spontaneous cancer development, especially in the liver and lung, respectively. Thus, lean and obese transgenic mice will also be evaluated for the tumor growth rate, inflammation and expression/activity of antioxidant enzymes. Finally, the understanding of this mechanism can contribute to the development of new therapeutic strategies and to prevent the progression of obesity-associated comorbidities.