Obesity promotes inflammation and immune responses in adipose tissue, leading to obesity-associated metabolic dysfunction and insulin resistance locally or systematically [
53]. Insulin resistance, as the significant basis of metabolic syndrome, closely links obesity with EC. The prevalence of insulin resistance in EC patients is high as reported to be 66.7% in one prospective study [
54]. However, increased BMI is significantly associated with higher risk of insulin resistance and in those women with BMI of 30 kg/m
2 or greater, this proportion reaches up to 84% [
54]. Insensitivity of target organs to insulin following insulin resistance results in hyperinsulinemia, impaired fasting glucose and could even develop into diabetes mellitus in severe cases. As the pathophysiological basis of metabolic syndrome, insulin resistance is closely correlated with EC. In one meta-analysis of 13 studies including 1562 EC patients and 2526 controls, fasting insulin level was significantly higher in women with EC [
55]. Hyperinsulinemia is associated with not only disordered proliferative endometrium as well as endometrial hyperplasia but also type I EC, indicating that it is involved in the development of endometrial hyperplastic lesions and EC [
56]. Xue et al. [
57,
58] found that increased serum insulin level was the independent risk factors for type I EC. Insulin resistance also indicates worse prognosis of EC patients. Wang et al. [
59] have reported that insulin resistance (OR 9.5, 95% CI 3.3–27.0), metabolic syndrome (OR 4.9, 95% CI 1.5–15.5), condition of both insulin resistance and metabolic syndrome (OR 21.0, 95% CI 4.8–92.7) is significantly associated with the recurrence in patients with atypical endometrial hyperplasia (AEH) and early EC, which may help predict the prognosis and optimize the therapeutic strategies for patients with fertility-sparing treatment. In terms of molecular mechanism, insulin is involved in the progression of EC directly or synergistically with other factors. The insulin receptor (InsR) and InsR substrate (IRS)-1 were found to be activated in EC tissues, which was associated with elevated serum insulin in EC [
60]. Insulin promotes EC cells proliferation, anti-apoptosis and invasion through PI3K/Akt and MEK/ERK pathway [
60,
61]. Insulin and estrogen synergistically promote type 1 EC progression through activating ER-α and InsR-β respectively and their downstream signaling pathways in a crosstalk way [
58,
62]. The estrogen sensitivity of EC cells could also be regulated in an insulin-dependent way. Insulin promotes estradiol-driven EC cells proliferation via up-regulating the expression of Ten-eleven-translocation 1 (TET1), which is a DNA hydroxymethylase that could enhance G-protein-coupled estrogen receptor (GPER) expression [
63]. GPER expression is strongly increased in tissues from EC patients with insulin resistance and also positively correlates with TET1 expression in EC tissues, which further indicate the role of insulin in the progression of EC mediated by TET1-driven GPER expression [
63].