Xiang Aoqi, Chu Guiyan, Zhu Youbo, Ma Guangjun, Yang Gongshe, Sun Shiduo
Laboratory of Animal Fat Deposition & Muscle Development, Department of Animal Science, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
J Cell Physiol. 2019 Sep;234(9):15288-15298. doi: 10.1002/jcp.28174. Epub 2019 Jan 26.
Excess intramyocellular lipids are often accompanied by muscle insulin resistance (IR) and type 2 diabetes. The mechanism of the formation of intramyocellular lipids is unclear yet. In this study, we optimized the cellular model of intramyocellular lipids from differentiated C2C12 cells and identified that the expression of insulin-like growth factor-binding protein 5 (IGFBP5) is diminished in this process. Then, we added exogenous recombinant IGFBP5 during myocyte triglyceride (TAG) formation and found decreased lipids accumulation. In addition, IGFBP5 could promote lipolysis when added to the cellular model after the formation of intramyocellular lipids. Moreover, IGFBP5 could enhance myocyte insulin sensitivity by inhibiting the expression of the thioredoxin-interacting protein (TXNIP) and arrestin domain-containing 4 (ARRDC4), which are a negative regulator of insulin signaling in both cases. Meanwhile, IGFBP5 also inhibited the expression of glycerol-3-phosphate acyltransferase (GPAM) and diglyceride acyltransferase 2 (DGAT2), which were involved in TAG synthesis from a fatty acid. IGFBP5 also reduced TAG storage by promoting lipolysis. Therefore, IGFBP5 may play a role in the excess accumulation of lipid in muscle cells of diabetic patients and serve as a reference for further research and treatment of muscle IR and diabetes.
肌细胞内脂质过多常伴有肌肉胰岛素抵抗（IR）和2型糖尿病。肌细胞内脂质形成的机制尚不清楚。在本研究中，我们优化了分化的C2C12细胞的肌细胞内脂质细胞模型，并确定胰岛素样生长因子结合蛋白5（IGFBP5）的表达在此过程中降低。然后，我们在肌细胞甘油三酯（TAG）形成过程中添加外源性重组IGFBP5，发现脂质积累减少。此外，在肌细胞内脂质形成后添加到细胞模型中时，IGFBP5可促进脂肪分解。此外，IGFBP5可通过抑制硫氧还蛋白相互作用蛋白（TXNIP）和含 Arrestin 结构域 4（ARRDC4）的表达来增强肌细胞胰岛素敏感性，这两种蛋白在两种情况下都是胰岛素信号的负调节因子。同时，IGFBP5还抑制了参与脂肪酸TAG合成的甘油-3-磷酸酰基转移酶（GPAM）和二酰甘油酰基转移酶2（DGAT2）的表达。IGFBP5还通过促进脂肪分解减少TAG储存。因此，IGFBP5可能在糖尿病患者肌肉细胞脂质过度积累中起作用，并为进一步研究和治疗肌肉IR和糖尿病提供参考。
