Regulation of beige adipocyte plasticity in inguinal white adipose tissue.

摘要 米色脂肪细胞可塑性指的是在生热活跃和非活跃状态之间转换的能力 与环境波动相适应。例如，寒冷诱导形成米色脂肪细胞，而 温暖的温度和过量的营养导致它们的消失。之前，我们已经描述过米色 白色脂肪细胞冷转化为米色脂肪细胞的脂肪细胞复兴现象 确实有Ucp1的表达历史(是Ucp1+-谱系)。有趣的是，米色脂肪细胞的复兴 受Ucp1--非细胞系白色脂肪细胞自主调节。 这一建议将进一步阐明米色脂肪细胞可塑性的细胞和分子机制。目标1 将研究HDAC4：PRDM16复合体在Ucp1-系白色脂肪细胞中的体内相关性 与米色脂肪细胞可塑性有关。目标2将确定HDAC4的调节机制：PRDM16 分子和染色质水平上的复杂依赖基因网络。目标3将开发潜在的贡献 细胞外基质重塑对维持Ucp1+系米色脂肪细胞的作用。先前的研究已经 表明在啮齿动物和人类中，米色脂肪细胞的活动与新陈代谢适应性之间存在相关性。 这一方向的研究可能为治疗肥胖和相关代谢提供新的可用药靶点。 精神错乱。

ABSTRACT Beige adipocyte plasticity refers to the ability to transform between thermogenic active and inactive states in accordance to environment fluctuations. For example, cold induces the formation of beige adipocytes, while warm temperature and nutrient excess lead to their disappearance. Previously, we have described the beige adipocyte renaissance phenomenon that the white adipocytes to be converted to beige adipocytes by cold indeed have Ucp1 expression history (being Ucp1+-lineage). Interestingly, beige adipocyte renaissance is regulated by Ucp1--lineage white adipocytes non-cell autonomously. This proposal will further delineate the cellular and molecular mechanisms of beige adipocyte plasticity. Aim 1 will investigate the in vivo relevance of HDAC4:PRDM16 complex in Ucp1--lineage white adipocytes that is relevant to beige adipocyte plasticity. Aim 2 will determine the regulatory mechanisms of HDAC4:PRDM16 complex-dependent gene network at molecular and chromatin levels. Aim 3 will exploit the potential contribution of extracellular matrix remodeling to the maintenance of Ucp1+-lineage beige adipocytes. Prior researches have suggested a correlation between activities of beige adipocytes and metabolic fitness in both rodents and humans. Investigations in this direction may provide novel druggable targets to treat obesity and related metabolic disorders.