Fig 1.

Effects of obesity on endometrial proliferation and tumorigenesis. Obesity contributes to the increased risk of endometrial cancer in the postmenopausal uterus by a variety of mechanisms. Increased adiposity increases aromatase activity, which leads to the conversion of androgens to estrogens, to directly promote endometrial proliferation and transcription of proproliferative genes. The chronic inflammation associated with visceral adiposity is mediated by proinflammatory adipokines and leads to hyperinsulinemia, increases in insulin-like growth factor 1 (IGF1), and hyperglycemia, which fuel endometrial proliferation. A concurrent decrease in anti-inflammatory cytokines is also observed. Inflammation and an increase in estrogen metabolites further contribute to DNA damage and genetic instability. Finally, stem cells can be recruited from adipose tissue, where they contribute to a supportive tumor microenvironment. ER, estrogen receptor; IGF1R, insulin-like growth factor 1 receptor; IR, insulin receptor; IRS, insulin receptor substrate; mTOR, mammalian target of rapamycin. (Illustration created by Suety Kwan).