Adipokine secretion

As an endocrine organ, adipose tissue produces an array of cytoactive compounds, including the aforementioned inflammatory cytokines, with biologic functions, which influence metabolism.

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Obesity alters the amount of these proteins secreted and they may individually or collectively influence the development of cancer.

Leptin is primarily produced by white adipose tissue and acts to indicate satiety. In obesity, there is both increased production and relative resistance leading to further increases in production. It has proinflammatory and proproliferative functions.59

Serum leptin is increased in patients with obesity, but there is no clear association with circulating levels in patients and cancer risk.60,61 A polymorphism which may alter serum leptin levels, LEP G2548A, has been associated in a meta-analysis with a small increased overall cancer risk (odds ratio 1.27, 95% CI 1.05–1.54).62

There appears to be an interplay between leptin and adiponectin, at least in experimental models of gastrointestinal cancers with downregulation of leptin-induced proliferation by adiponectin in both hepatocellular63 and esophageal carcinomas.64

Adiponectin is an abundant cytokine secreted by adipocytes in visceral fat depots, but levels are inversely associated with obesity.65

Adiponectin has antiangiogenic and anti-inflammatory properties, and in animal models, it inhibits tumor growth.66 Circulating levels are reduced in patients with postmenopausal breast cancer67–69 and appear to be correlated with survival outcomes.70

Decreased expression of adiponectin is closely correlated with insulin resistance,71,72 and which mechanism is more closely correlated with carcinogenesis is unclear.

Adiponectin may also reduce expression of proinflammatory cytokines such as NFκB by reducing the growth of macrophages73 and other proteins via AMP kinase-induced downregulation of the proproliferative mTOR pathway.74,75

In animal models, low serum adiponectin levels are associated with increased development of hepatic76 and colorectal adenomas.77 Adiponectin serum levels are inversely associated with colorectal cancer risk as shown by a meta-analysis (odds ratio 0.716, 95% CI 0.606–0.847),78 but this finding was not independent of either BMI or waist circumference.