RT - Journal Article T1 - The effects of exercise on changes of adipokines secreted by adipose tissue in women with breast cancer JF - RJMS YR - 2021 JO - RJMS VO - 28 IS - 8 UR - http://rjms.iums.ac.ir/article-1-7007-en.html SP - 76 EP - 89 K1 - Breast cancer K1 - Exercise K1 - Adipose tissue K1 - Adipokines AB - Background & Aims: Breast cancer is the most common tumor in women and is the second leading cause of death from cancer after lung cancer. This type of cancer accounts for 25% of all cancers and 12% of cancer-related deaths and is associated with invasion, metastasis and high recurrence rates, especially metastatic capacity of the brain and lungs (1). Over the past 3 decades, patient survival has increased due to advances in treatment and diagnosis. However, patients' quality of life is still negatively affected by the side effects of chemotherapy. Targeted and hormonal therapies do not have long-term effects in most cases, and some patients resist treatment with a significant reduction in therapeutic effect. Epidemiological and etiological evidence show that aberrant fat is a significant factor and a negative prognostic factor for breast cancer (2). Adipose tissue plays an essential role as an energy storage medium and can act as endocrine cells to produce various active substances (3). In addition, studies have confirmed that adipocytes adjacent to invasive cancer cells, referred to as cancer-related fat cells, are involved in the development of breast cancer (4). Breast tissue is composed of 90% adipose tissue with permanent interactions between epithelial cells and fat cells (5). Adipocytes and their precursor mesenchymal stem cells (MSCs) may maintain tumor phenotypes by acting as energy reservoirs for neighboring cancer cells or by secreting signaling molecules and vesicles containing proteins, lipids, and nucleic acids (6). For a long time, adipose tissue was considered an energy source. Today, it is well established that adipose tissue plays a major role in metabolism as a member of the endocrine glands responsible for secreting biologically active molecules called adipokines. Adipokines have hormonal function and as growth factors that modulate insulin resistance, regulate fat and glucose metabolism, and participate in pro-inflammatory and anti-inflammatory responses (7). Adipokines are classified as hormones, growth factors, angiogenic factors, and cytokines. Among them, leptin, adiponectin, resistin and chemerin have the most studies (10). Exercise has many benefits for healthy and unhealthy populations. Repetition of exercise not only directly plays an important role in the prevention of breast cancer (incidence rate), controlling the progression of breast cancer and improving the patient's physical abilities and balance, but also indirectly reduces fatigue and nausea and increases Self-esteem and quality of life in patients with breast cancer (11). Epidemiological studies have shown that exercise can regulate factors that increase the risk of breast cancer, thus reducing the incidence and mortality of breast cancer (12,13). Breast cancer is still a major medical, social and economic problem due to its increasing prevalence and adverse treatment outcomes. Numerous scientific reports show the benefits of physical activity on various pathophysiological aspects of breast cancer. Changes in adipokines secreted by adipose tissue in response to exercise can increase insights into proposing an appropriate exercise strategy to improve the function of hormone secreted by adipose tissue in breast cancer. In this review, we will discuss the importance of breast adipose tissue and then discuss the different roles of breast adipose tissue in the development and progression of breast cancer. Then we deal with adipokines secreted from adipose tissue and the response of these adipokines to sports activities. According to the above, the present study intends to investigate the effects of exercise on changes of adipokines secreted by adipose tissue in women with breast cancer. Methods: Search for studies on the changes of adipokines in response to exercise in breast cancer in articles published in the reputable databases Springer, Hindawi, PubMed, Google Scholar, Scopus, SID and ISC using the keyword Exercise Training, adipokines (Leptin, adiponectin, resistin and chemerin) were performed. 16 studies of adipokines responses to exercise in women with breast cancer were reviewed. Results: In many studies, the regulation of adipokines secreted by adipose tissue, including increase in adiponectin and decrease in leptin and resistin levels, was observed in women with breast cancer. Also, Exercise interventions that reduce fat mass modulate the concentration of adipokines. Conclusion: Most research on the relationship between fat and adipokines has been on the progression of breast cancer (68-70). Also, Positive correlations have been reported for waist-hip ratio, waist circumference, or other indicators of obesity and breast cancer risk in women (71). Exercise is a safe and effective adjunctive treatment for breast cancer. Exercise can affect body fat and composition if energy intake equals or exceeds energy absorption. Because adipokines are secreted from adipose tissue, any exercise intervention that reduces fat may be desirable (56). However, it is important to note that energy expenditure during exercise, independent of fat reduction, can also improve the regulation of adipokines, and this strategy can ultimately improve the prognosis of breast cancer (13). Considering the levels of adipokines studied, it was found that the changes in all these biomarkers are, at least indirectly, related to body size. Therefore, the effect of exercise can be entirely or partially dependent on weight loss (50). One of the chronic adaptations resulting from exercise is the regulation of the production and secretion of adipokines, which leads to beneficial molecular adaptation in adipose tissue and immune cells. Therefore, exercise is responsible for changes in adipose tissue function that are able to reverse the metabolic disorder observed in the breast cancer population. Studies have shown that the greatest effect on adipokines is achieved with long-term exercise, 12 weeks or more (45-50, 54, 56). Regardless of the greater understanding of the mechanisms by which exercise beneficially modulates adipokine concentrations in breast cancer, physicians should continue to support exercise as an adjunct to breast cancer because exercise alters the net balance of most obesity-related hormones Therefore, beneficial modification of the tumor microenvironment ultimately improves the quality of life and clinical outcomes of patients. As mentioned, after reviewing research on exercise and its effects on adipokines in breast cancer, it was found that increased energy intake, regardless of fat reduction, may play an important role in improving hormonal factors in the tumor microenvironment. Otherwise increases breast tumorigenesis. Therefore, future research should focus on determining the role of energy consumption and its potential mechanisms in reducing adipokine concentrations in obese breast cancer populations. Interactions between biomarkers should also be considered in future etiological studies, while exercise interventions should examine the effects of exercise independently of weight loss, various exercise prescriptions, and effects on central obesity. In general, based on the limited evidence to date, more research is needed to elucidate the response of adipokines to exercise interventions and their possible role in breast cancer. In summary, most studies have reported the regulation of adipokines secreted by adipose tissue, including an increase in adiponectin and a decrease in leptin and resistin levels in women with breast cancer. Also, the reduction of fat mass due to exercise interventions was associated with modulating the concentration of adipokines. Therefore, it is suggested to emphasize the need for exercise in breast cancer. LA eng UL http://rjms.iums.ac.ir/article-1-7007-en.html M3 ER -