Response gene to complement 32 suppresses adipose tissue thermogenic genes through inhibiting 3-adrenergic receptor/mTORC1 signaling
Response gene to complement 32 suppresses adipose tissue thermogenic genes through inhibiting 3-adrenergic receptor/mTORC1 signaling
复制标题
DOI：
10.1096/fj.201701508r
复制
发表时间：
2018-09-01
期刊：
影响因子：
4.8
通讯作者：
Chen, Shi-You
中科院分区：
文献类型：
--
作者：
Chen, Sisi;Mei, Xiaohan;Chen, Shi-You
我们以前的研究表明，补体反应基因（RGC）-32缺陷（Rgc 32（-/-））保护小鼠免受饮食诱导的肥胖，并增加脂肪组织中产热基因的表达。然而，RGC-32调节产热基因表达的潜在机制仍有待确定。在本研究中，RGC-32在白色脂肪组织（WAT）中的表达在冷胁迫诱导的WAT布朗宁过程中受到抑制。Rgc 32（-/-）显著增加腹股沟（i）WAT和肩胛间棕色脂肪组织（BAT）的分化基质血管部分（SVF）中的产热基因表达。Rgc 32（-/-）和冷暴露调节iWAT中的一组常见基因，如RNA测序数据所示。途径富集分析显示Rgc 32（-/-）下调PI 3 K/Akt信号相关基因。Rgc 32（-/-）iWAT中Akt磷酸化也持续降低，导致3-肾上腺素能受体（3-AR）表达增加，随后激活哺乳动物雷帕霉素靶蛋白复合物（mTORC）-1。3-AR拮抗剂SR 59230 A和mTORC 1抑制剂雷帕霉素阻断了iWAT和肩胛间BAT中Rgc 32（-/-）诱导的产热基因表达。这些结果表明，RGC-32通过PI 3 K/Akt依赖性机制下调3-AR表达和mTORC 1活性来抑制脂肪组织产热基因表达。梅，X.，Yin，A.，Yin，H.，崔，X。- B.，陈思Y.补体32应答基因通过抑制3-肾上腺素能受体/mTORC 1信号传导抑制脂肪组织产热基因。
Our previous studies have shown that response gene to complement (RGC)-32 deficiency (Rgc32(-/-)) protects mice from diet-induced obesity and increases thermogenic gene expression in adipose tissues. However, the underlying mechanisms by which RGC-32 regulates thermogenic gene expression remain to be determined. In the present study, RGC-32 expression in white adipose tissue (WAT) was suppressed during cold exposure-induced WAT browning. Rgc32(-/-) significantly increased thermogenic gene expression in the differentiated stromal vascular fraction (SVF) of inguinal (i)WAT and interscapular brown adipose tissue (BAT). Rgc32(-/-) and cold exposure regulated a common set of genes in iWAT, as shown by RNA sequencing data. Pathway enrichment analyses showed that Rgc32(-/-) down-regulated PI3K/Akt signaling-related genes. Akt phosphorylation was also consistently decreased in Rgc32(-/-) iWAT, which led to an increase in 3-adrenergic receptor (3-AR) expression and subsequent activation of mammalian target of rapamycin complex (mTORC)-1. 3-AR antagonist SR 59230A and mTORC1 inhibitor rapamycin blocked Rgc32(-/-)-induced thermogenic gene expression in both iWAT and interscapular BAT. These results indicate that RGC-32 suppresses adipose tissue thermogenic gene expression through down-regulation of 3-AR expression and mTORC1 activity via a PI3K/Akt-dependent mechanism.Chen, S., Mei, X., Yin, A., Yin, H., Cui, X.-B., Chen, S.-Y. Response gene to complement 32 suppresses adipose tissue thermogenic genes through inhibiting 3-adrenergic receptor/mTORC1 signaling.