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肝脏 X 受体(LXR)在代谢性疾病中的分子生物学和功能基因组学。

Molecular biology and functional genomics of liver X receptors (LXR) in relationship to metabolic diseases.

机构信息

Department of Biosciences and Nutrition, Novum, Karolinska Institutet, S-141 83 Huddinge, Sweden.

出版信息

Curr Opin Pharmacol. 2010 Dec;10(6):692-7. doi: 10.1016/j.coph.2010.07.003. Epub 2010 Sep 9.

Abstract

The metabolic syndrome constitutes a group of metabolic conditions that increase the risk of developing diseases, including cardiovascular disease (CVD) and type 2 diabetes (T2D). LXRα/β are regulators of lipogenesis, cholesterol/glucose homoeostasis and inflammatory pathways, processes that are intertwined with development of the metabolic syndrome. The employment of LXRs as pharmaceutical targets for treatment of various aspects of the metabolic syndrome has been promptly investigated but serious side effects, like hepatic steatosis, have hampered this process. Novel treatment regimes now focus on development of isoform-specific or tissue-specific LXR agonist/antagonist compounds to circumvent effects on lipid biosynthesis. Other strategies to explore the beneficial aspects of LXR activation include targeting co-factors or pathways that are modifying LXR activity.

摘要

代谢综合征是一组代谢性疾病,会增加患心血管疾病 (CVD) 和 2 型糖尿病 (T2D) 等疾病的风险。LXRα/β 是脂肪生成、胆固醇/葡萄糖稳态和炎症途径的调节剂,这些过程与代谢综合征的发展交织在一起。LXR 作为治疗代谢综合征各个方面的药物靶点已被迅速研究,但严重的副作用,如肝脂肪变性,阻碍了这一过程。目前的治疗方案侧重于开发同工型特异性或组织特异性 LXR 激动剂/拮抗剂化合物,以避免对脂质生物合成的影响。探索 LXR 激活有益方面的其他策略包括针对调节 LXR 活性的辅助因子或途径。

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