Common mechanisms of dysfunctional adipose tissue and obesity‐related cancers

Abstract

The relation between cancer and metabolic disorders was recognized several decades ago, but the underlying mechanisms involved in cancer development and progression remain obscure. In the last years, many groups have been studying systemic adipose tissue markers in cancer patients. However, few consistent results were obtained. On the other hand, several studies revealed many aspects of adipose tissue physiology in obesity. Nowadays, it is recognized that excessive lipid uptake in adipocytes leads to hypertrophy and consequently to metabolic dysregulation, hypoxia, inflammation, impaired adipocytokine expression and angiogenesis, insulin resistance and macrophage recruitment. In obese patients, tumours commonly colocalize with excessive adipose tissue accumulation, and most of the features of hypertrophic adipose tissue are observed in cancer patients, namely breast and colon. This review aimed to summarize pathological adipose tissue alterations that may contribute to cancer aetiology and development.

Deregulated microRNAs and Adiponectin in Postmenopausal Women with Breast Cancer

“…It was observed that in BC patients, visceral fat rating was associated with some BC characteristics, including hormone receptor status and tumor stage at diagnosis. The increase of visceral adipose tissue has been associated with hyperinsulinemia and insulin resistance, factors associated with an increase in BC risk [8]. Insulin exerts a direct mitogenic effect on BC cells, has a synergistic activity with estrogens, and can indi- rectly affect tumorigenesis by contributing to the synthesis and activity of IGFs I and II.…”

Secreted factors derived from obese visceral adipose tissue regulate the expression of breast malignant transformation genes

“…A number of hypotheses have been proposed to explain this link 2, 3 , including the high production of several factors, such as adipokines and inflammatory cytokines, by excess adipose tissue in the obese individuals 3,10,11 . In obesity, adipose tissue becomes dysfunctional, which results in metabolic and inflammatory changes that increase oxidative stress and the production of reactive oxygen species (ROS).…”

Obesity and cancer: the role of adipose tissue and adipo-cytokines-induced chronic inflammation

“…Finally, HIF-1a was associated with an increase occurrence of metastases. Furthermore HIF-1a inhibition might improve sensitivity of tumors to radiation 37,41.…”

“…There is an axis between white hypertrophic adipocytes secreting inflammatory proteins and functional status of the endothelium of the capillaries and systemic fat 125. The inflammatory proteins secreted by hypertrophic and hypoxic white adipocytes are the primary cause of atherosclerosis, state of insulin resistance, high blood pressure, type 2 diabetes mellitus, metabolic syndrome, bone joint and muscle tendon degeneration 126-128. Furthermore links between obesity and inflammation and between chronic inflammation and cancer may suggest that inflammation may be important in linking obesity to cancer 129-132.…”