Molecular Pathways: Adipose Inflammation as a Mediator of Obesity-Associated Cancer

摘要: The increasing rate of obesity worldwide is predicted to be associated with a surge in diseases. Notably, has been linked approximately 20% cancer cases the United States; both increased risk and worse outcomes after diagnosis. Altered levels circulating factors are strongly implicated, including insulin, insulin-like growth factor 1, leptin, adiponectin, interleukin-6 (IL-6). In addition, attention focused on consequences local adipose inflammation. Inflammatory foci characterized by crown-like structures consisting dead adipocytes encircled macrophages occur white depots, breast tissue, most overweight obese women. Saturated fatty acids, released as consequence obesity-associated lipolysis, induce macrophage activation via Toll-like receptor 4, thereby stimulating NF-κB signaling. This, turn, activates transcription proinflammatory genes COX-2, IL-6, IL-1β, TNFα. Elevated mediators cause systemic effects. Of particular relevance regard CYP19 gene encoding aromatase, rate-limiting enzyme for estrogen synthesis. this obesity-inflammation-aromatase axis provides plausible explanation rates postmenopausal, hormone receptor-positive hence may offer targets interventions attenuate or improve prognosis. Potential approaches include weight reduction, exercise, suppression obesity-driven signaling pathways using pharmaceutical dietary agents. A key future goal identify biomarkers that accurately report inflammation, identification at-risk individuals assess efficacy interventions. Clin Cancer Res; 19(22); 6074-83. ©2013 AACR.