Transcriptome profiling reveals divergent expression shifts in brown and white adipose tissue from long-lived GHRKO mice.
Transcriptome profiling reveals divergent expression shifts in brown and white adipose tissue from long-lived GHRKO mice.
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转录组谱图揭示了长寿命GHRKO小鼠的棕色和白色脂肪组织的不同表达转移。
DOI：
10.18632/oncotarget.5760
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发表时间：
2015-09-29
期刊：
影响因子：
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通讯作者：
Masternak MM
中科院分区：
文献类型：
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作者：
Stout MB;Swindell WR;Zhi X;Rohde K;List EO;Berryman DE;Kopchick JJ;Gesing A;Fang Y;Masternak MM
由于生长激素信号传导的丧失，缺乏生长激素受体（GHRKO）的小鼠表现出更长的寿命和健康寿命。 GHRKO 小鼠中棕色和白色脂肪组织（BAT 和 WAT）的分布和活性均发生改变，但每种组织对年龄相关表型的贡献仍不清楚。因此，我们使用全基因组微阵列来评估 GHRKO 和六个月龄正常同窝小鼠之间 BAT 和 WAT 库的转录差异。我们的研究结果揭示了独特的 BAT 转录组以及 BAT 对 Ghr 消融的独特反应。 GHRKO 小鼠的 BAT 表现出与线粒体和代谢相关的基因表达升高，同时单核细胞衍生细胞（树突状细胞 [DC] 和巨噬细胞）表达的基因表达降低。在 WAT 中观察到的情况基本上相反，DC 表达的基因表达增加，而与代谢、细胞呼吸和线粒体内膜相关的基因表达减少。这些发现表明，BAT 和 WAT 对 GHRKO 小鼠中 GH 信号丢失的反应模式不同。这些模式表明，BAT 和 WAT 以不同的方式对 GHRKO 小鼠的表型做出贡献，Ghr 消融会减弱 BAT 中的炎症，以及 WAT 中的细胞代谢和线粒体生物发生。
Mice lacking the growth hormone receptor (GHRKO) exhibit improved lifespan and healthspan due to loss of growth hormone signaling. Both the distribution and activity of brown and white adipose tissue (BAT and WAT) are altered in GHRKO mice, but the contribution of each tissue to age-related phenotypes has remained unclear. We therefore used whole-genome microarrays to evaluate transcriptional differences in BAT and WAT depots between GHRKO and normal littermates at six months of age. Our findings reveal a unique BAT transcriptome as well as distinctive responses of BAT to Ghr ablation. BAT from GHRKO mice exhibited elevated expression of genes associated with mitochondria and metabolism, along with reduced expression of genes expressed by monocyte-derived cells (dendritic cells [DC] and macrophages). Largely the opposite was observed in WAT, with increased expression of DC-expressed genes and reduced expression of genes associated with metabolism, cellular respiration and the mitochondrial inner envelope. These findings demonstrate divergent response patterns of BAT and WAT to loss of GH signaling in GHRKO mice. These patterns suggest both BAT and WAT contribute in different ways to phenotypes in GHRKO mice, with Ghr ablation blunting inflammation in BAT as well as cellular metabolism and mitochondrial biogenesis in WAT.