State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
Biochem Biophys Res Commun. 2022 Jan 15;588:111-117. doi: 10.1016/j.bbrc.2021.12.039. Epub 2021 Dec 15.
The ovariectomy would induce the occurrence of obesity, but its regulatory mechanism is not clear. This study aimed to elucidate the regulation on fat accumulation for ovariectomy in mouse. In the current study, the abdominal fat mass dramatically increased in OVX mice compared with sham mice at eighth week after ovariectomy, accompanied with the higher GnRH level in blood and abdominal fat tissue. Also, a decrease of the abdominal fat mass was occurred in OVX mice with a GnRH-antagonist injection. Furthermore, the results in vivo and in vitro confirmed that GnRH promoted the transition of G1/S phase by upregulating CCND1 and CCNE1 mRNA levels by the mediation of GnRHR via the PKA-CREB pathway. Meanwhile, the higher FSH secretion was induced by increase GnRH and accelerate fat deposition in abdominal fat tissue. Our findings are the first to elucidate the effect mechanism of ovariectomy on obesity in mouse. GnRH stimulates fat accumulation in adipocytes via PKA-CREB pathway by directly promoting cell proliferation for driving the cell cycle and simultaneously accelerating differentiation for improving the FSH secretion.
去卵巢会导致肥胖的发生，但具体的调控机制尚不清楚。本研究旨在阐明去卵巢对小鼠脂肪积累的调控机制。在本研究中，与假手术组相比，去卵巢 8 周后的 OVX 小鼠的腹部脂肪量明显增加，同时血液和腹部脂肪组织中的 GnRH 水平升高。此外，用 GnRH 拮抗剂注射的 OVX 小鼠的腹部脂肪量减少。此外，体内和体外的结果证实，GnRH 通过 GnRHR 介导的 PKA-CREB 通路，上调 CCND1 和 CCNE1 mRNA 水平，促进 G1/S 期的转变，从而促进脂肪细胞的增殖，进而促进脂肪的沉积。同时，GnRH 水平的升高会促进 FSH 的分泌，从而加速腹部脂肪组织的脂肪沉积。我们的研究结果首次阐明了 GnRH 刺激脂肪细胞增殖和分化，进而促进脂肪沉积的作用机制，为肥胖的治疗提供了新的靶点。
