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您的检索式：作者名="Shimeng Xuan"
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| 1 | Blocking FSH inhibits hepatic cholesterol biosynthesis and reduces serum cholesterol显示文摘Menopause is associated with dyslipidemia and an increased risk of cardio-cerebrovascular disease.The classic view assumes that the underlying mechanism of dyslipidemia is attributed to an insufficiency of estrogen.In addition to a decrease in estrogen, circulating follicle-stimulating hormone (FSH)levels become elevated at menopause.In this study,we find that blocking FSH reduces serum cholesterol via inhibiting hepatic cholesterol biosynthesis.First,epidemiological results show that the serum FSH levels are positively correlated with the serum total cholesterol levels,even after adjustment by considering the effects of serum estrogen,in addition,the prevalence of hypercholesterolemia is significantly higher in peri-menopausal women than that in premenopausal women.Furthermore,we generated a mouse model of FSH elevation by intraperitoneally injecting exogenous FSH into ovariectomized (OVX)mice,in which a normal level of estrogen (E2)was maintained by exogenous supplementation. Consistently,the results indicate that FSH,independent of estrogen,increases the serum cholesterol level in this mouse model. Moreover,blocking FSH signaling by anti-FSHβ antibody or ablating the FSH receptor (FSHR)gene could effectively prevent hypercholesterolemia induced by FSH injection or high-cholesterol diet feeding.Mechanistically,FSH,via binding to hepatic FSHRs, activates the Gi2α/β-arrestin-2/Akt pathway and subsequently inhibits the binding of FoxO1 with the SREBP-2 promoter,thus preventing FoxO1 from repressing SREBP-2 gene transcription.This effect,in turn,results in the upregulation of SREBP-2,which drives HMGCR nascent transcription and de novo cholesterol biosynthesis,leading to the increase of cholesterol accumulation.This study uncovers that blocking FSH signaling might be a new strategy for treating hypercholesterolemia during menopause, particularly for women in peri-menopause characterized by FSH elevation only. | Yanjing Guo Meng Zhao Tao Bo Shizhan Ma Zhongshang Yuan Wenbin Chen Zhao He Xu Hou Jun Liu Zhenhai Zhang Qiang Zhu Qiangxiu Wang Xiaoyan Lin Zhongli Yang Min Cui Lu Liu Yujie Li Chunxiao Yu Xiaoyi Qi Qian Wang Haiqing Zhang Qingbo Guan Lifang Zhao Shimeng Xuan Huili Yan Yanliang Lin Li Wang Qihang Li Yongfeng Song Ling Gao Jiajun Zhao | 2019 | Cell Research2019，29，2： | 16 |
| 2 | Perilipin 2 and lipid droplets provide reciprocal stabilization显示文摘The lipid droplet (LD)-associated protein adipose differentiation-related protein (ADRP or PLIN2) is required for the formation and stability of the LD organelle, whereas its biological roles are still obscure. Herein, we show that PLIN2 is the most abundant protein on the lipid droplets (LDs) of mouse myoblast cell line C2C12. Both the expression of PLIN2 and the accumulation of LDs were up-regulated in a time- and dose-dependent manner when the cells were treated with oleate (OA). The protein level of PLIN2 was positively correlated with the formation of LDs, suggesting that LDs stabilize PLIN2. Furthermore, knocking out PLIN2 in C2C12 cells led to enlarged LDs and higher triacylglycerol hydrolysis activity. The isolated PLIN2 null LDs became closely contact w让h mitochondria and other cellular organelles. Additionally mitochondrial activity was suppressed by OA in PLIN2 null cells. Our results reveal the pivotal roles of PLIN2 in governing LD dynamics and their relationship to mitochondria, and suggest a reciprocal stabilization between PLIN2 and LDs. | Shimeng Xu Fei Zou Zhiqing Diao Shuyan Zhang Yaqin Deng Xiaotong Zhu Liujuan Cui Jinhai Yu Zhiguang Zhang Adekunle Toyin Bamigbade Hongchao Zhang Xuan Wei Xuelin Zhang Bin Liang Pingsheng Liu | 2019 | Biophysics Reports2019，5，3： | 1 |
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