Muscle-specific downregulation of GR levels inhibits adipogenesis in porcine intramuscular adipocyte tissue.
Muscle-specific downregulation of GR levels inhibits adipogenesis in porcine intramuscular adipocyte tissue.
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DOI：
10.1038/s41598-017-00615-9
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发表时间：
2017-03-30
影响因子：
4.6
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Chu W;Wei W;Han H;Gao Y;Liu K;Tian Y;Jiang Z;Zhang L;Chen J
肌内脂肪有利于猪肉品质的提高，而皮下脂肪在猪生产中被认为是废物。因此，揭示这两种脂肪的调节差异有助于脂肪沉积的组织特异性控制。在这项研究中，我们发现，与皮下脂肪细胞（SA）相比，肌内脂肪细胞（IMA）对糖皮质激素（GC）的敏感性较低。糖皮质激素受体（GR）的比较显示IMA的GR水平较低，这可能是其降低GCs敏感性的原因之一。与SA相比，IMA中GR启动子1-C和1-H的甲基化水平较高。肌肉条件培养液（MCM）处理后，脂肪细胞GR表达降低，导致脂肪细胞增殖和分化受到明显抑制。由于ELISA法检测到MCM中含有丰富的肌生成抑制素（MSTK），我们进一步研究了这种肌生成抑制素对脂肪细胞的作用。MCM处理抑制脂肪细胞GR表达、细胞增殖和分化，其作用类似于MCM。甲基化水平的GR启动子1-C和1-H也升高后，MIPH处理。我们的研究揭示了GR在肌纤维抑制肌内脂肪细胞中的作用，并确定肌肉生长抑制素作为肌肉源性脂肪GR水平的调节剂。
Intramuscular adipose is conducive to good pork quality, whereas subcutaneous adipose is considered as waste in pig production. So uncovering the regulation differences between these two adiposes is helpful to tissue-specific control of fat deposition. In this study, we found the sensitivity to glucocorticoids (GCs) was lower in intramuscular adipocytes (IMA) compared with subcutaneous adipocytes (SA). Comparison of glucocorticoid receptor (GR) revealed that IMA had lower GR level which contributed to its reduced GCs sensitivity. Higher methylation levels of GR promotor 1-C and 1-H were detected in IMA compared with SA. GR expression decrease was also found in adipocytes when treated with muscle conditioned medium (MCM) in vitro, which resulted in significant inhibition of adipocytes proliferation and differentiation. Since abundant myostatin (MSTN) was detected in MCM by ELISA assay, we further investigated the effect of this myokine on adipocytes. MSTN treatment suppressed adipocytes GR expression, cell proliferation and differentiation, which mimicked the effects of MCM. The methylation levels of GR promotor 1-C and 1-H were also elevated after MSTN treatment. Our study reveals the role of GR in muscle fiber inhibition on intramuscular adipocytes, and identifies myostatin as a muscle-derived modulator for adipose GR level.