Pathway Preferential Estrogens Prevent Hepatosteatosis Due to Ovariectomy and High-Fat Diets.
Pathway Preferential Estrogens Prevent Hepatosteatosis Due to Ovariectomy and High-Fat Diets.
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DOI：
10.3390/nu13103334
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发表时间：
2021-09-23
期刊：
影响因子：
5.9
通讯作者：
Madak-Erdogan Z
中科院分区：
文献类型：
--
作者：
Zuo Q;Chen KL;Arredondo Eve A;Liu YJ;Kim SH;Katzenellenbogen BS;Katzenellenbogen JA;Madak-Erdogan Z
大约20-30%的绝经前妇女患有代谢综合征，绝经后妇女的人数几乎是绝经后妇女的两倍，这些妇女患脂肪肝的风险增加。患有代谢综合征的绝经后妇女通常用激素替代疗法（HRT）治疗，但目前可用的HRT中的雌激素增加了乳腺癌和子宫内膜癌以及心血管疾病的风险。因此，迫切需要找到更安全的替代HRT来改善绝经后代谢健康。途径优先雌激素1（PaPE-1）是一种新的雌激素受体配体，已显示其有利地影响代谢组织而对生殖组织没有不利影响。在这项研究中，我们研究了PaPE-1对代谢健康的影响，特别是在两种不同的小鼠模型中研究了其对肝脏转录组和血浆代谢物的影响：饮食诱导的肥胖（DIO）和瘦素缺乏（ob/ob）小鼠。PaPE-1显著降低DIO和ob/ob模型的肝脏重量和脂质蓄积，并降低与脂肪酸代谢和胶原沉积相关的基因的表达。此外，PaPE-1显著增加线粒体基因的表达，特别是与电子传递链相关的基因，表明能量消耗增加。使用转录组学和代谢组学数据的综合途径分析表明，PaPE-1治疗降低了炎症、胶原沉积和调节脂肪酸代谢的途径，并增加了与谷胱甘肽代谢相关的代谢物。总的来说，我们的研究结果支持PaPE-1的有益代谢作用，并表明PaPE-1可以保护绝经后妇女免受脂肪肝疾病的影响，而不会增加生殖系统癌症的风险。
About 20–30% of premenopausal women have metabolic syndrome, and the number is almost double in postmenopausal women, and these women have an increased risk of hepatosteatosis. Postmenopausal women with metabolic syndrome are often treated with hormone replacement therapy (HRT), but estrogens in currently available HRTs increase the risk of breast and endometrial cancers and Cardiovascular Disease. Therefore, there is a critical need to find safer alternatives to HRT to improve postmenopausal metabolic health. Pathway preferential estrogen 1 (PaPE-1) is a novel estrogen receptor ligand that has been shown to favorably affect metabolic tissues without adverse effects on reproductive tissues. In this study, we have examined the effects of PaPE-1 on metabolic health, in particular, examining its effects on the liver transcriptome and on plasma metabolites in two different mouse models: diet-induced obesity (DIO) and leptin-deficient (ob/ob) mice. PaPE-1 significantly decreased liver weight and lipid accumulation in both DIO and ob/ob models and lowered the expression of genes associated with fatty acid metabolism and collagen deposition. In addition, PaPE-1 significantly increased the expression of mitochondrial genes, particularly ones associated with the electron transport chain, suggesting an increase in energy expenditure. Integrated pathway analysis using transcriptomics and metabolomics data showed that PaPE-1 treatment lowered inflammation, collagen deposition, and pathways regulating fatty acid metabolism and increased metabolites associated with glutathione metabolism. Overall, our findings support a beneficial metabolic role for PaPE-1 and suggest that PaPE-1 may protect postmenopausal women from fatty liver disease without increasing reproductive cancer risk.
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禁止素-1通过调节线粒体功能和衰老来维持内皮细胞的血管生成能力。
影响因子：
7.8
作者：
Schleicher, Michael;Shepherd, Benjamin R.;Suarez, Yajaira;Fernandez-Hernando, Carlos;Yu, Jun;Pan, Yong;Acevedo, Lisette M.;Shadel, Gerald S.;Sessa, William C.
通讯作者：
Sessa, William C.
影响因子：
5.8
作者：
Wagner, JD;Thomas, MJ;Cefalu, WT
通讯作者：
Cefalu, WT
影响因子：
7.3
作者：
Madak-Erdogan Z;Kim SH;Gong P;Zhao YC;Zhang H;Chambliss KL;Carlson KE;Mayne CG;Shaul PW;Korach KS;Katzenellenbogen JA;Katzenellenbogen BS
通讯作者：
Katzenellenbogen BS
影响因子：
4.2
作者：
Ito, Makoto;Suzuki, Jun;Kanatani, Akio
通讯作者：
Kanatani, Akio
影响因子：
13.5
作者：
Feldstein, AE;Werneburg, NW;Gores, GJ
通讯作者：
Gores, GJ