丁酸钠通过激活cAMP通路在脂肪肝细胞模型中增加线粒体生成及脂肪氧化

Sodium butyrate promotes mitochondria biogenesis and lipid oxidation through activating cAMP pathway in fatty liver cell model

目的探讨丁酸钠对肝脏细胞代谢保护作用机制以及其与线粒体功能的关系。方法采用1c1c7肝细胞进行实验,检测线粒体及脂肪氧化相关转录基因、蛋白表达以及三磷酸腺苷(ATP)生成。首先使用棕榈酸对细胞进行培养检测线粒体相关基因;其后使用棕榈酸+丁酸钠共培养细胞并将其对线粒体和氧化相关基因的效应与棕榈酸单独培养相对照;接着单独以丁酸钠处理细胞后观察其对线粒体功能和线粒体相关复合体蛋白的变化趋势;最后检测丁酸钠处理细胞后线粒体功能相关的环磷酸腺苷(cAMP)通路变化趋势。结果棕榈酸可导致线粒体功能相关PGC-1α转录受抑;相反,加入丁酸钠与其共培养处理后细胞线粒体及氧化相关功能基因转录增强;使用丁酸钠培养细胞后线粒体蛋白复合体2转录增加,线粒体ATP生成明显增加;1c1c7细胞使用丁酸钠培养后,线粒体功能相关的cAMP通路有相应变化,我们发现p-CREB表达增加同时PDE3B受抑制,表明cAMP通路的激活。结论丁酸钠可能通过cAMP通路介导其对肝脏脂肪变性中线粒体功能的保护作用。

Objective To investigate the mechanism underlying the effect of sodium butyrate on protecting liver metabolism and its relationship with mitochondrial function. Methods The 1c1c7 cells were chosen for subsequent experiment. The expression levels of mitochondria and lipid oxidation-related genes and proteins and the production of adenosine triphosphate (ATP) were quantitatively detected. The 1c1c7 cells were cultured by palmitic acid to detect mitochondria-related genes. Subsequently, the cells were co-cultured with palmitic acid combined with sodium butyrate. The effect of palmitic acid combined with sodium butyrate and palmitic acid alone upon the mitochondria and lipid oxidation-related genes was statistically compared. The variation trend of mitochondrial function and mitochondria-related complex protein was observed after the cells were treated with sodium butyrate alone. The changes of the mitochondrial function-related cyclic adenosine monophosphate (cAMP) signaling pathway were detected following sodium butyrate treatment. Results Palmitic acid suppressed the translation of mitochondrial function-related PGC-1α. Conversely, palmitic acid combined with sodium butyrate treatment enhanced the translation of mitochondria and lipid oxidation-related genes. The translation of mitochondrial protein complex 2 and the production of mitochondrial ATP were strengthened after sodium butyrate treatment. The changes of mitochondrial function-related cAMP signaling pathway were observed after the 1c1c7 cells were cultured with sodium butyrate. The expression of p-CREB was up-regulated, whereas that of PDE3B was down-regulated, suggesting that the cAMP signaling pathway was activated. Conclusion Sodium butyrate probably mediates the protective effect upon the mitochondrial function via the cAMP signaling pathway in the in fatty liver cell model.