Effect of High-fat Diet-induced Disorders on Rat with Endometrial Hyperplasia and Adiponectin System in Circulation and Uterus

Background: Epidemiologic and genetic studies suggest a link between insulin resistance (IR) and endometrial cancer, and endometrial hyperplasia (EH) is a precancerous stage of endometrial cancer. Adiponectin is an adipokine which previously shown to be a risk factor for endometrial cancer. The aim of the study was to develop a rat model of IR and EH and evaluate adiponectin system in circulation and uterus. Methods: This study was a 46-week animal trial from February 2014 to January 2015. Female Sprague-Dawley rats were fed with high-fat diet (HFD) for 40 weeks to induce IR. Followed by ovariectomization, rats were orally administrated to 17 beta-estradiol (E-2) for 4 weeks to induce EH and then sacrificed. A total of 36 rats were divided into four groups: E-2, HFD, HFD + E-2, and control groups. Data were analyzed with Student's t-test, one-way analysis of variance (ANOVA), and Mann-Whitney U-tests. Chi-square was used to evaluate the score of immunohistochemistry. Results: The thickness of endometrial, glandular epithelium, and myometrium in the HFD-E-2 group were higher than the E-2 group (F = 59.02, F = 23.51 and F = 12.53, respectively, all P < 0.001). Plasma adiponectin levels in the E-2 group were lower than those in the control group, and the levels in the HFD-E-2 group were lower than those in the HFD group (F = 13.15, P < 0.05). However, after normalized to visceral adipose tissue, compared to the control group, plasma adiponectin levels were decreased in rat with HFD in the absence or presence of E-2, respectively (F = 6.72, P < 0.05). Adiponectin gene (F = 10.48, P < 0.05) and protein (P < 0.05) levels in uterus in the HFD-E-2 group were higher than those in the HFD group. Conclusions: This study manifests that IR can effectively modulate EH, which suggests the involvement of energetic metabolism in uterine alternation. The combination effects of IR and EH modulate circulating adiponectin levels. However, adiponectin gene and protein levels in uterus are mainly response to estradiol.