Regulation of beige adipocyte plasticity in inguinal white adipose tissue.

腹股沟白色脂肪组织中米色脂肪细胞可塑性的调节。

• 批准号: 10563617
• 负责人: Biao Wang
• 金额: $ 57.27万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-21 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10563617
• 关键词: Abbreviations; Ablation; Adipocytes; Adipose tissue; Adult; Affect; Age; Automobile Driving; Back; Brown Fat; Catecholamines; Cell Nucleus; Cells; Characteristics; Chromatin; Complex; Cues; Environment; Extracellular Matrix; Fibrosis; Genetic; Genetic Transcription; HDAC4 gene; Histone Deacetylase; Homeostasis; Human; Immune; In Vitro; Investigation; Knowledge; Lead; Maintenance; Metabolic; Metabolic Diseases; Molecular; Mus; Nutrient; Obesity; Obesity Epidemic; Pathway interactions; Performance; Physiological; Process; Production; Property; Recording of previous events; Regulation; Renaissance; Repression; Research; Resolution; Rodent; SET Domain; Signal Transduction; Sumoylation Pathway; System; Temperature; Tissues; Transforming Growth Factor beta; Work; clinical application; environmental change; gene network; genetic corepressor; in vivo; lipid biosynthesis; metabolic fitness; mouse model; new therapeutic target; novel; novel therapeutic intervention; postnatal; preservation; prevent; progenitor; programs; receptor; response; uncoupling protein 1; warm temperature

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.

抽象的 米色脂肪细胞可塑性是指在生热活性和非活性状态之间转换的能力 根据环境波动。例如，寒冷会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。之前我们已经描述过米色 脂肪细胞复兴现象，即白色脂肪细胞受冷转变为米色脂肪细胞 确实有 Ucp1 表达历史（即 Ucp1+-谱系）。有趣的是，米色脂肪细胞的复兴是 受Ucp1-谱系白色脂肪细胞非细胞自主调节。 该提议将进一步描述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 复合物在 Ucp1 中的体内相关性 - 谱系白色脂肪细胞是 与米色脂肪细胞可塑性相关。目标2将确定HDAC4:PRDM16的调控机制 分子和染色质水平上复杂依赖的基因网络。目标 3 将利用潜在贡献 细胞外基质重塑对 Ucp1+ 谱系米色脂肪细胞维持的影响。先前的研究有 表明米色脂肪细胞的活动与啮齿动物和人类的代谢健康之间存在相关性。 这个方向的研究可能会提供新的药物靶标来治疗肥胖和相关代谢 失调。