Regulation of beige adipocyte plasticity in inguinal white adipose tissue.

摘要 脂肪细胞可塑性是指脂肪细胞在产热活性和非活性状态之间转换的能力， 根据环境波动。例如，冷诱导米色脂肪细胞的形成，而 温暖的温度和营养过剩导致它们消失。此前，我们已经描述了米色 脂肪细胞再生现象，即白色脂肪细胞在低温下转变为米色脂肪细胞 确实具有Ucp 1表达历史（是Ucp 1+谱系）。有趣的是，米色脂肪细胞的再生 受Ucp 1调节--谱系白色脂肪细胞非细胞自主。 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。要求1 将研究HDAC 4：PRDM 16复合物在Ucp 1-谱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。目的2将确定HDAC 4：PRDM 16的调节机制 在分子和染色质水平上的复合物依赖的基因网络。目标3将利用潜在的贡献 细胞外基质重塑对维持Ucp 1+谱系米色脂肪细胞的影响。先前的研究有 表明在啮齿动物和人类中米色脂肪细胞的活动与代谢适应性之间存在相关性。 这一方向的研究可能会提供新的药物靶点，以治疗肥胖和相关的代谢紊乱。 紊乱

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.