Figure 1. Multiple factors influence carcinogenesis in obesity.
Chronic anabolism and inflammation are central sequelae of the many alterations in multiple organ systems observed in obesity. Direct effects of increased nutrient and metabolite delivery to cells promote cellular anabolism and proliferation, and directly stimulate the immune system via TLR and other receptor families. Increased systemic inflammation promotes cell damage, turnover, and mutagenesis. Cytokines, adipokines, steroids, and gut hormones are elevated in obesity and similarly promote cellular anabolism and proliferation and inflammation. Adipocytes within formal adipose tissue depots, as well as ectopic adipocytes present in virtually all tissues, contribute by providing nutrients, adipokines, and cytokines to all cells via paracrine and endocrine mechanisms. Tumors, once established, recruit adipocytes and adipocyte stem cells to enhance these effects. All of these pathways trigger ER and oxidative stress pathways which in turn perpetuate one another, leading to a vicious cycle of cell stress. The combination of anabolism and inflammation creates a systemic milieu that predisposes to carcinogenesis.