Osteocalcin improves nonalcoholic fatty liver disease in mice through activation of Nrf2 and inhibition of JNK
Osteocalcin improves nonalcoholic fatty liver disease in mice through activation of Nrf2 and inhibition of JNK
复制标题
骨钙素通过激活 Nrf2 和抑制 JNK 改善小鼠非酒精性脂肪肝
DOI：
10.1007/s12020-016-0926-5
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发表时间：
2016-09-01
期刊：
影响因子：
3.7
通讯作者：
Jia, Weiping
中科院分区：
文献类型：
--
作者：
Du, Jing;Zhang, Mingliang;Jia, Weiping
最近的研究表明，骨钙素对非酒精性脂肪性肝病（NAFLD）的保护作用，但具体的潜在机制尚不清楚。Nrf 2和JNK通路在NAFLD的发病机制中起重要作用。本研究旨在研究骨钙素是否通过调节这些途径来预防NAFLD。雄性C57/BL 6 J小鼠喂食高脂饮食12周以诱导NAFLD，并在此期间通过每日腹膜内注射用重组脱羧骨钙素（30 ng/g）或载体处理。骨钙素治疗保护小鼠免受饮食诱导的肝脏甘油三酯积累和肝损伤。由于骨钙素的干预，喂食高脂饮食的小鼠肝脏中丙二醛和8-异前列腺素F2 α水平升高以及氧化型谷胱甘肽与还原型谷胱甘肽的比率升高显著降低。骨钙素处理不仅激活了Nrf 2核转位，上调了抗氧化酶基因（过氧化氢酶，SOD和GPx）的表达，而且抑制了肝脏中JNK的激活。GPRC 6A是骨钙素的假定受体，在肝脏中发现。总之，这些结果表明，骨钙素通过激活Nrf 2通路减轻氧化应激和抑制JNK通路来改善NAFLD。
Recent studies have demonstrated a protective effect of osteocalcin against nonalcoholic fatty liver disease (NAFLD), although the specific underlying mechanisms remain unclear. Nrf2 and JNK pathways play important roles in the pathogenesis of NAFLD. The present study aimed to investigate whether osteocalcin protects against NAFLD by regulating these pathways. Male C57/BL6J mice were fed a high-fat diet for 12 weeks to induce NAFLD and were treated with recombinant decarboxylate osteocalcin (30 ng/g) or vehicle by daily intraperitoneal injection during this period. Osteocalcin treatment protected mice from diet-induced hepatic triglyceride accumulation and liver injury. Increased levels of malondialdehyde and 8-iso-prostaglandin F2 alpha as well as a higher ratio of oxidized to reduced glutathione in the liver of mice fed a high-fat diet were significantly decreased due to the intervention of osteocalcin. Osteocalcin treatment not only activated Nrf2 nuclear translocation and up-regulated the expression of antioxidant enzyme genes (catalase, SOD, and GPx), but also inhibited the activation of JNK in the liver. GPRC6A, the putative receptor of osteocalcin, was found in the liver. In conclusion, these results suggest that osteocalcin improves NAFLD by activating the Nrf2 pathway to alleviate oxidative stress and inhibiting JNK pathway.