Papel da obesidade induzida por dieta hiperlipídica no desenvolvimento de carcinoma mamário experimental

Abstract

Obesity has become a public health problem. A large number of diseases, including cardiovascular disease, type 2 diabetes and various cancers, including breast cancer in post-menopausal women, are associated with obesity. Breast cancer is the mainly cause of cancer- related deaths in women in developed countries and its incidence has increased throughout the developing countries. Most deaths associated with breast cancer results from uncontrolled metastatic disease. Thus, is important to investigate changes in lifestyle, including dietary habits that are able to decrease the risk of developing breast cancer and metastasis. In this work, we investigate the potential development of 4T1 mammary carcinoma and metastases in mice subjected to a high fat diet. BALB/c, females, aged 4-6 weeks were fed with standard diet where 10% of kcal from fat or high-fat diet where 60% of kcal from fat; for 6 or 16 weeks. Body weight, feed intake and biochemical profile were analyzed. At the end of this period, mice of both groups received the 4T1 lineage tumor cells. The weight and volume of tumor and the development of bone metastases were examined. The profile of proinflammatory cytokines TNF-α and IL-6 as well as leptin was also evaluated. It has been observed a body weight gain of the animals fed the HFD, without increasing the feed intake from the second weeks of diet. After 16 weeks of diet, the obese animals showed increased perigonadal and retroperitoneal fat. Moreover, they demonstrated reduced glucose tolerance, increased leptin and cholesterol serum levels. After receiving the tumor cells, the survival of obese animals fed for 16 weeks, although not significant, was lower. These animals also showed tumors bulkier and heavier, and increase bone metastases. The cytokine profile of obese animals that received tumor, already at an advanced stage of the disease, with the development of secondary tumors, has also changed. We observed decreased expression of leptin, accompanied by decreased IL-6 and TNF-α. Our results, taken together, show that eating a high-fat diet can induce obesity in BALB/c mice and may promote the progression of breast cancer.