Adipose tissue dysfunction and its effects on tumor metabolism

Abstract

Growing by an alarming rate in the Western world, obesity has become a condition associated with a multitude of diseases such as diabetes, metabolic syndrome and various cancers. Generally viewed as an abnormal accumulation of hypertrophied adipocytes, obesity is also a poor prognostic factor for recurrence and chemoresistance in cancer patients. With more than two-thirds of the adult population in the United States considered clinically overweight or obese, it is critical that the relationship between obesity and cancer is further emphasized and elucidated. Adipocytes are highly metabolically active cells, which, through release of adipokines and cytokines and activation of endocrine and paracrine pathways, affect processes in neighboring and distant cells, altering their normal homeostasis. This work will examine specifically how adipocyte-derived factors regulate the cellular metabolism of malignant cells within the tumor niche. Briefly, tumor cells undergo metabolic pressure towards a more glycolytic and hypoxic state through a variety of metabolic regulators and signaling pathways, i.e., phosphoinositol-3 kinase (PI3K), hypoxia-inducible factor-1 alpha (HIF-1α), and c-MYC signaling. Enhanced glycolysis and high lactate production are hallmarks of tumor progression largely because of a process known as the Warburg effect. Herein, we review the latest literature pertaining to the body of work on the interactions between adipose and tumor cells, and underlining the changes in cancer cell metabolism that have been targeted by the currently available treatments.

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

“…In obesity, adipose tissue hypoxia may cause cellular mechanisms that lead to the development of insulin resistance, to a state of chronic inflammation with infiltration of macrophages, the reduction of adiponectin and increased of leptin, adipocyte death, ER stress and mitochondrial dysfunction 30-34. Therefore, adipose tissue hypoxia might contribute to cancer risk in the obese population 35,36. Hypoxia-inducible factor 1 alpha (HIF-1a), is an important transcription factor that is regulated by hypoxia and in tumors leads to increased vascularization.…”

To assess the association between vertebral marrow fat content and colorectal adenoma in postmenopausal women using magnetic resonance spectroscopy

“…However, there are several possible explanations for the link between marrow fat content and colorectal adenoma. First, no longer considered as just a ''space filler'', marrow fat is recognized as a highly active organ, functions of which extend far beyond the storage of triglycerides and lipid metabolism, and they serve as an insulin-sensitive endocrine tissue that affects bone mass, energy expenditure, and insulin metabolism (24,25). Bone metabolism itself might have a direct effect on the development of colorectal adenoma (26).…”

Obesity as a Promoter of Cancer Development and Progression

“…The TME can also induce hypoxia via anaerobic respiration, even in the presence of oxygen [46]. Under hypoxic conditions, ASCs are recruited to the tissue and are stimulated to secrete VEGF.…”