Chu Weiwei, Wei Wei, Yu Shigang, Han Haiyin, Shi Xiaoli, Sun Wenxing, Gao Ying, Zhang Lifan, Chen Jie
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, PR China.
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, PR China; College of Public Health, Nantong University, Nantong 226019, PR China.
Biochem Biophys Res Commun. 2016 Mar 25;472(1):68-74. doi: 10.1016/j.bbrc.2016.02.063. Epub 2016 Feb 17.
Obesity is a well-established risk factor to health for its relationship with insulin resistance, diabetes and metabolic syndrome. Myocyte-adipocyte crosstalk model plays a significant role in studying the interaction of muscle and adipose development. Previous related studies mainly focus on the effects of adipocytes on the myocytes activity, however, the influence of myotubes on the preadipocytes development remains unclear. The present study was carried out to settle this issue. Firstly, the co-culture experiment showed that the proliferation, cell cycle, and differentiation of 3T3-L1 preadipocytes were arrested, and the apoptosis was induced, by differentiated C2C12 myotubes. Next, the sensitivity of 3T3-L1 preadipocytes to glucocorticoids (GCs), which was well known as cell proliferation, differentiation, apoptosis factor, was decreased after co-cultured with C2C12 myotubes. What's more, our results showed that C2C12 myotubes suppressed the mRNA and protein expression of glucocorticoid receptor (GR) in 3T3-L1 preadipocytes, indicating the potential mechanism of GCs sensitivity reduction. Taken together, we conclude that C2C12 myotubes inhibited 3T3-L1 preadipocytes proliferation and differentiation by reducing the expression of GR. These data suggest that decreasing GR by administration of myokines may be a promising therapy for treating patients with obesity or diabetes.
肥胖因其与胰岛素抵抗、糖尿病和代谢综合征的关系,是一个已被充分证实的健康风险因素。心肌细胞-脂肪细胞相互作用模型在研究肌肉与脂肪发育的相互作用中起着重要作用。先前的相关研究主要关注脂肪细胞对心肌细胞活性的影响,然而,肌管对前脂肪细胞发育的影响仍不清楚。本研究旨在解决这一问题。首先,共培养实验表明,分化的C2C12肌管可使3T3-L1前脂肪细胞的增殖、细胞周期和分化停滞,并诱导其凋亡。其次,与C2C12肌管共培养后,3T3-L1前脂肪细胞对糖皮质激素(GCs)的敏感性降低,而糖皮质激素是众所周知的细胞增殖、分化和凋亡因子。此外,我们的结果表明,C2C12肌管抑制了3T3-L1前脂肪细胞中糖皮质激素受体(GR)的mRNA和蛋白表达,这表明了糖皮质激素敏感性降低的潜在机制。综上所述,我们得出结论,C2C12肌管通过降低GR的表达抑制了3T3-L1前脂肪细胞的增殖和分化。这些数据表明,通过给予肌动蛋白减少GR可能是治疗肥胖或糖尿病患者的一种有前景的疗法。