Lmo4-resistin signaling contributes to adipose tissue-liver crosstalk upon weight cycling
Lmo4-resistin signaling contributes to adipose tissue-liver crosstalk upon weight cycling
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Lmo4 - 抵抗素信号传导有助于体重循环时的脂肪组织 - 肝脏串扰
DOI：
10.1096/fj.201902708r
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发表时间：
2020-02-06
期刊：
影响因子：
4.8
通讯作者：
Zheng，Ling
中科院分区：
文献类型：
--
作者：
Sun，Yu;Geng，Mengyuan;Zheng，Ling
当人们试图减肥时，经常会看到体重减轻和恢复的重复循环，称为体重循环。确切的病理生理效应和体重循环的潜在机制仍不清楚。在这里，我们报告了通过在1周转换方案中交替喂食低脂肪饮食或高脂肪饮食的小鼠诱导的体重循环，与连续HF喂食的小鼠相比，导致附睾白色脂肪组织（eWAT）重量、前脂肪细胞增殖、肝脏炎症、空腹血糖水平和葡萄糖耐受不良进一步增加。将分泌蛋白数据库与RNA测序和定量PCR（qPCR）结果相结合，发现eWAT中几种脂肪因子的mRNA水平，包括Retn（编码Retn），因体重循环而改变。发现转录辅因子Lmo 4受体重循环调节; Lmo 4增强3 T3-L1细胞中前脂肪细胞增殖、体外脂肪形成、Retn转录和Retn分泌。原代小鼠肝细胞给予重组小鼠Ign（rm-Ign），或暴露于Lmo 4-过表达的3 T3-L1细胞的培养基，显示炎症反应和增生增加。此外，注射rm-abrin的正常食物喂养的小鼠显示通过增加新生血管生成上调血糖水平，并上调肝脏炎症反应。总之，我们的研究结果表明Lmo 4 ‐ pectin信号在体重循环中的调节作用，表明脂肪组织和肝脏之间的串扰。
Repeated cycles of weight loss and regain, known as weight cycling, is often seen when people try to lose weight. The exact pathophysiological effects and the underlying mechanisms of weight cycling remain largely unclear. Here, we report that weight cycling induced by alternating feeding mice with a low‐fat diet or a high‐fat diet in a 1‐week switch protocol caused further increased epididymal white adipose tissue (eWAT) weight, preadipocyte proliferation, hepatic inflammation, fasting blood glucose level, and glucose intolerance, compared with the continuously HF‐fed mice. Combining the secretory protein database with RNA‐sequencing and quantitative PCR (qPCR) results in eWAT, the mRNA levels of several adipokines, including Retn (encoding resistin), were found altered by weight cycling. A transcriptional co‐factor Lmo4 was found regulated by weight cycling; Lmo4 enhanced preadipocyte proliferation, in vitro adipogenesis, transcription of Retn, and resistin secretion in 3T3‐L1 cells. Primary mouse hepatocytes administrated with recombinant mouse resistin (rm‐resistin), or exposed to media from Lmo4‐overexpressed 3T3‐L1 cells, showed increased inflammatory responses and gluconeogenesis. Furthermore, rm‐resistin‐injected normal chow‐fed mice showed upregulated blood glucose level by increasing gluconeogenesis, and upregulated the hepatic inflammatory responses. Together, our results suggest a regulatory role of Lmo4‐resistin signaling in weight cycling, indicating a crosstalk between the adipose tissue and liver.