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. 2017 Aug 5;130(15):1831-1837.
doi: 10.4103/0366-6999.211551.

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

Chen-Guang Shang  1 , Zhao-Hui Liu  1 , Xiao-Hui Wang  1 , Zong-Hao Feng  1 , Yan Zhang  1
Affiliations

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

Chen-Guang Shang et al. Chin Med J (Engl). .

Abstract

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 17β-estradiol (E2) for 4 weeks to induce EH and then sacrificed. A total of 36 rats were divided into four groups: E2, HFD, HFD + E2, 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-E2group were higher than the E2group (F = 59.02, F = 23.51 and F = 12.53, respectively, all P < 0.001). Plasma adiponectin levels in the E2group were lower than those in the control group, and the levels in the HFD-E2group 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 E2, 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-E2group 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.

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Conflict of interest statement

There are no conflicts of interest.

Figures

Figure 1
Figure 1
Representative microscopic images of Hematoxylin and Eeosin staining in uterus tissues (original magnification, ×400). The black arrows point to the high column endometrium. (a) Control group, standard diet + sham-ovariectomized + vehicle; (b) E2 group, standard diet + ovariectomized + 17β-estradiol; (c) HFD group, high-fat diet + ovariectomized + vehicle; (d) HFD-E2 group, high-fat diet + ovariectomized + 17β-estradiol.
Figure 2
Figure 2
Plasma adiponectin and relative plasma adiponectin concentration after high-fat diet and 17β-estradiol treatment. (a) Plasma adiponectin; (b) plasma adiponectin after normalized to visceral adipose tissue. Data represent the mean ± standard error. *P < 0.05. n = 9 in each group. Control: Standard diet + sham-ovariectomized + vehicle; E2: Standard diet + ovariectomized + 17β-estradiol; HFD: High-fat diet + ovariectomized + vehicle; HFD-E2: High-fat diet + ovariectomized + 17β-estradiol.
Figure 3
Figure 3
Relative mRNA levels of adiponectin (a), adiponectin receptor 1 (b), and adiponectin receptor 2 (c) in rat uterus. Results represent the mean ± standard error. *P < 0.05. n = 9 in each group. Control: Standard diet + sham-ovariectomized + vehicle; E2: Standard diet + ovariectomized + 17β-estradiol; HFD: High-fat diet + ovariectomized + vehicle; HFD-E2: High-fat diet + ovariectomized + 17β-estradiol.
Figure 4
Figure 4
Immunohistochemical analysis of adiponectin and AdipoR1 and AdipoR2 expression in rat endometrium (original magnification, ×400). The black arrows point to adiponectin protein positive staining in endometrium. n = 9 in each group. Control: Standard diet + sham-ovariectomized + vehicle; E2: Standard diet + ovariectomized + 17β-estradiol; HFD: High-fat diet + ovariectomized + vehicle; HFD-E2: High-fat diet + ovariectomized + 17β-estradiol; AdipoR: Adiponectin receptor.
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