Abstract
Newly emerging data highlight obesity as an important risk factor for developing certain types of cancer, including colorectal cancer. Although evidence supports a link between the two, the mechanisms responsible for this relationship have not yet been fully elucidated. Hypertrophied and dysfunctional adipose tissue of the obese state is characterized by low-grade inflammation. Adipokines and cytokines secreted from adipocytes, together with the abundant availability of lipids from adipocytes in the tumor microenvironment, promote adhesion, migration, and invasion of tumor cells and support tumor progression and uncontrolled growth. One of the predisposed targets of the deleterious effects exerted by secretions from adipose tissue in obesity is the activities associated with the cellular mitochondria. Mitochondrial oxidative metabolism plays a key role in meeting cells’ energetic demands by oxidative phosphorylation (OxPhos). Here we discuss: (a) the dynamic relationship between glycolysis, the tricarboxylic acid cycle, and OxPhos; (b) the evidence for impaired OxPhos (i.e., mitochondrial dysfunction) in colon cancer; (c) the mechanisms by which mitochondrial dysfunction can predispose to cancer. We propose that impaired OxPhos increases susceptibility to colon cancer since OxPhos is sensitive to a large number of factors that are intrinsic to the host (e.g., inflammation). Given that adipocytes are a major source of adipokines and energy for the cancer cell, understanding the mechanisms of metabolic symbiosis between cancer cells and adipocytes should reveal new therapeutic possibilities.
Highlights
Emerging data highlight obesity as an important risk factor for developing certain types of cancer, including colorectal cancer
We recently addressed the issue of metabolic reprograming in obesity-associated Colorectal cancer (CRC) and demonstrated that secreted products from the adipose tissue of obese subjects inhibit mitochondrial respiration and function in HCT116 colon cancer cells, an effect that is at least partly mediated by leptin [82]
In our recent study [82], we demonstrate that colon cancer cells exposed to conditioned media prepared from VAT from obese subjects express lower oxygen consumption rate (OCR) levels than colon cancer cells exposed to conditioned media obtained from VAT from lean subjects
Summary
Emerging data highlight obesity as an important risk factor for developing certain types of cancer, including colorectal cancer. The substantial infiltration of inflammatory cells into the adipose tissue of obese subjects induces a stage of chronic inflammation that modifies the local metabolism, and influences systemic energy homeostasis [19]. Most of the inflammatory cells in the obese individual’s adipose tissue are activated macrophages that release a wide variety of proinflammatory cytokines such as MCP-1, TNF-α, IL-6, IL-8, and others.
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