Department of Environmental Health, Faculty of Human Life and Environment, Nara Women's University, Kitauoya Nishimachi, Nara 630-8506, Japan.
Department of Health and Nutrition, Faculty of Health Science, Kyoto Koka Women's University, 38 Kadono-cho, Nishikyogoku, Ukyo-ku, Kyoto 615-0882, Japan.
Nutrients. 2020 Mar 26;12(4):907. doi: 10.3390/nu12040907.
This study aims to investigate the effects of estradiol replacement on the orexigenic action of ghrelin in ovariectomized (OVX) obese rats fed with a high-fat diet (HFD). Four weeks after OVX at 9 weeks of age, Wistar rats were subcutaneously implanted with either 17β-estradiol (E2) or placebo (Pla) pellets and started on HFD feeding. After 4 weeks, growth hormone-releasing peptide (GHRP)-6, a growth hormone secretagogue receptor (GHSR) agonist injected intraperitoneally, induced changes in HFD intake, and c-Fos-positive neurons in the hypothalamic arcuate nucleus (ARC) were measured in both groups. The ghrelin protein and mRNA levels, as well as GHSR protein in stomach, were analyzed by Western blotting and real-time PCR. HFD increased energy intake and body weight in the Pla group, while it temporarily reduced these in the E2 group. GHRP-6 enhanced HFD intake and activated neurons in the ARC only in the Pla group. Furthermore, gastric ghrelin and GHSR protein levels were lower in the E2 group than in the Pla group, but plasma acyl ghrelin levels were similar in both groups. Our results suggest that E2 replacement improves obesity by inhibiting the orexigenic action of ghrelin via downregulation of ghrelin and its receptor in stomach in HFD-fed OVX rats.
本研究旨在探讨雌激素替代对高脂饮食喂养去卵巢肥胖大鼠胃促生长素（ghrelin）摄食作用的影响。9 周龄时行去卵巢（OVX）手术 4 周后，Wistar 大鼠皮下植入 17β-雌二醇（E2）或安慰剂（Pla）微球，并开始给予高脂饮食（HFD）喂养。4 周后，腹腔内注射生长激素释放肽（GHRP）-6，一种生长激素促分泌素受体（GHSR）激动剂，观察 HFD 摄入量的变化，并测量下丘脑弓状核（ARC）中 c-Fos 阳性神经元。通过 Western blot 和实时 PCR 分析胃中 ghrelin 蛋白和 mRNA 水平以及 GHSR 蛋白。HFD 增加了 Pla 组的能量摄入和体重，而在 E2 组中，这种作用暂时减少。GHRP-6 仅在 Pla 组中增强了 HFD 的摄入和 ARC 神经元的激活。此外，E2 组的胃 ghrelin 和 GHSR 蛋白水平低于 Pla 组，而两组的血浆酰基 ghrelin 水平相似。我们的结果表明，E2 替代通过下调 HFD 喂养 OVX 大鼠胃中的 ghrelin 和其受体，抑制 ghrelin 的摄食作用，从而改善肥胖。
