Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, China.
Tongji School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
FASEB J. 2020 Mar;34(3):4732-4748. doi: 10.1096/fj.201902708R. Epub 2020 Feb 6.
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.
反复的体重减轻和反弹，称为体重循环，当人们试图减肥时经常出现。体重循环的确切病理生理效应和潜在机制在很大程度上仍不清楚。在这里，我们报告了一种通过在 1 周的转换方案中交替喂养高脂肪饮食或低脂肪饮食的小鼠来诱导体重循环的方法，与连续高脂肪喂养的小鼠相比，这种方法导致附睾白色脂肪组织（eWAT）重量、前体脂肪细胞增殖、肝炎症、空腹血糖水平和葡萄糖耐量进一步增加。将分泌蛋白数据库与 RNA 测序和定量 PCR（qPCR）结果相结合，我们发现在 eWAT 中，几种脂肪因子的 mRNA 水平发生了改变，包括编码抵抗素的 Retn。转录共因子 Lmo4 被发现受到体重循环的调节；Lmo4 增强了 3T3-L1 细胞中的前体脂肪细胞增殖、体外脂肪生成、Retn 和抵抗素分泌的转录。用重组鼠抵抗素（rm-resistin）或暴露于过表达 Lmo4 的 3T3-L1 细胞培养基处理的原代小鼠肝细胞显示出增加的炎症反应和糖异生。此外，rm-resistin 注射的正常饮食喂养的小鼠通过增加糖异生导致血糖水平升高，并上调肝炎症反应。总之，我们的结果表明 Lmo4-抵抗素信号在体重循环中起调节作用，表明脂肪组织和肝脏之间存在串扰。
