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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Both liver-X receptor (LXR) isoforms control energy expenditure by regulating Brown Adipose Tissue activity
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Both liver-X receptor (LXR) isoforms control energy expenditure by regulating Brown Adipose Tissue activity

机译：两种肝X受体（LXR）亚型均通过调节棕色脂肪组织的活性来控制能量消耗

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摘要

Brown adipocytes are multilocular lipid storage cells that play a crucial role in nonshivering thermogenesis. Uncoupling protein 1 (UCP1) is a unique feature of brown fat cells that allows heat generation on sympathetic nervous system stimulation. As conventional transcriptional factors that are activated in various signaling pathways, liver-X receptors (LXRs) play important roles in many physiological processes. The role of LXRs in the regulation of energy homeostasis remains unclear, however. Female WT, LXRαβ~(-/-), LXRα~(-/-), and LXRβ~(-/-) mice were fed with either a normal diet (ND) or a high-carbohydrate diet (HCD) supplemented with or without GW3965-LXR agonist. LXRαβ~(-/-) mice exhibited higher energy expenditure (EE) as well as higher UCP1 expression in brown adipose tissue (BAT) compared with WT mice on the HCD. In addition, long-term treatment of WT mice with GW3965 showed lower EE at thermoneutrality (30 ℃) and lower Ucp1 expression level in BAT. Furthermore, H&E staining of the BAT of LXRαβ~(-/-) mice exhibited decreased lipid droplet size compared with WT mice on the HCD associated with a more intense UCP1-positive reaction. Quantification of triglyceride (TG) content in BAT showed lower TG accumulation in LXRβ~(-/-) mice compared with WT mice. Surprisingly, GW3965 treatment increased TG content (twofold) in the BAT of WT and LXRα~(-/-) mice but not in LXRβ~(-/-) mice. Furthermore, glucose transporter (GLUT4) in the BAT of LXRα~(-/-) and LXRβ~(-/-) mice was sixfold and fourfold increased, respectively, compared with WT mice on the ND. These findings suggest that LXRa as well as LXRp could play a crucial role in the regulation of energy homeostasis in female mice and may be a potential target for the treatment of obesity and energy regulation.
机译：棕色脂肪细胞是多细胞脂质存储细胞，在非颤抖的生热中起关键作用。解偶联蛋白1（UCP1）是棕色脂肪细胞的独特功能，可在交感神经系统刺激下产生热量。作为在各种信号传导途径中被激活的常规转录因子，肝X受体（LXR）在许多生理过程中起着重要作用。然而，LXR在能量稳态中的作用尚不清楚。给雌性WT，LXRαβ（-/-），LXRα〜（-/-）和LXRβ〜（-/-）小鼠补充或补充正常饮食（ND）或高碳水化合物饮食（HCD）没有GW3965-LXR激动剂。与HCD上的WT小鼠相比，LXRαβ〜（-/-）小鼠在棕色脂肪组织（BAT）中表现出更高的能量消耗（EE）和更高的UCP1表达。此外，用GW3965长期治疗WT小鼠在热中性（30℃）时EE降低，BAT中Ucp1表达水平降低。此外，与WT小鼠相比，LXRαβ〜（-/-）小鼠的BAT的H＆E染色显示脂质滴大小减小，且UCP1阳性反应更强烈。与野生型小鼠相比，BAT中甘油三酸酯（TG）含量的定量显示，LXRβ〜（-/-）小鼠的甘油三酯蓄积较低。出人意料的是，GW3965处理增加了WT和LXRα〜（-/-）小鼠的BAT中的TG含量（两倍），但没有增加LXRβ〜（-/-）小鼠的TG含量。此外，与ND小鼠相比，LXRα〜（-/-）和LXRβ〜（-/-）小鼠的BAT中的葡萄糖转运蛋白（GLUT4）分别增加了6倍和4倍。这些发现表明LXRa和LXRp可能在雌性小鼠能量稳态调节中起关键作用，并且可能是治疗肥胖症和能量调节的潜在靶标。

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    Marion Korach-Andre; Amena Archer; Rodrigo P. Barros; Paolo Parini; Jan-Ake Gustafsson;

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    Department of Biosciences and Nutrition at NOVUM, Karolinska Institutet, 14183 Huddinge, Sweden;

    Department of Biosciences and Nutrition at NOVUM, Karolinska Institutet, 14183 Huddinge, Sweden;

    Center for Nuclear Receptors and Cell Signaling,Department of Cell Biology and Biochemistry, University of Houston, TX 77204;

    Department of Biosciences and Nutrition at NOVUM, Karolinska Institutet, 14183 Huddinge, Sweden,Division of Clinical Chemistry, Department of Laboratory Medicine,Karolinska Institutet at Karolinska University Hospital, 14186, Huddinge, Sweden;

    Department of Biosciences and Nutrition at NOVUM, Karolinska Institutet, 14183 Huddinge, Sweden,Center for Nuclear Receptors and Cell Signaling,Department of Cell Biology and Biochemistry, University of Houston, TX 77204;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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