1-脱氧野尻霉素对肥胖小鼠肝细胞线粒体合成与自噬能力的改善作用  

1-Deoxynojirimycin Promotes Hepatocyte Mitochondrial Biosynthesis and Mitophagy in Obese Mice

作　　者：李思远 宁俊丽 丁晓雯[1] 黄先智[2] LI Siyuan;NING Junli;DING Xiaowen;HUANG Xianzhi(College of Food Science,Southwest University,Chongqing 400716,China;State Key Laboratory of Silkworm Genome Biology,Southwest University,Chongqing 400716,China)

机构地区：[1]西南大学食品科学学院,重庆400716 [2]西南大学家蚕基因组生物学国家重点实验室,重庆400716

出　　处：《食品科学》2020年第19期170-178,共9页Food Science

基　　金：现代农业产业技术体系建设专项(CARS-22)。

摘　　要：线粒体是机体重要的能量代谢场所,在调节脂代谢方面发挥着十分重要的作用。本实验研究1-脱氧野尻霉素(1-deoxynojirimycin,DNJ)对肥胖小鼠肝细胞线粒体合成与自噬的影响,探究DNJ对脂代谢影响的新途径。通过饲喂高脂饲料建立肥胖小鼠模型,肥胖小鼠继续饲喂高脂饲料的同时灌胃剂量分别为2.0、4.0、8.0 mg/(kg m_b·d)的DNJ 45 d,随后测定相关指标。结果表明,与肥胖对照组相比,经高剂量DNJ灌胃后,雌、雄肥胖小鼠的体质量增加减缓,炎症程度降低,雌雄小鼠血清脂联素水平分别上升43.19%、29.58%(P<0.01),雌鼠成纤维细胞生长因子21(fibroblast growth factor 21,FGF21)水平上升37.03%(P<0.01),雄鼠FGF21抵抗现象得到改善;雌、雄鼠腺苷酸活化蛋白激酶α1 mRNA表达上调,高剂量组雌、雄小鼠与线粒体合成有关的过氧化物酶体增殖物激活受体γ共激活剂1α、核呼吸因子1以及线粒体自噬关键蛋白unc-51样激酶1的mRNA表达上调,相应的蛋白水平分别上升28.27%、43.99%(P<0.01),50.25%、40.26%(P<0.01)和19.24%、22.76%(P<0.05);雌、雄鼠肉碱棕榈酰转移酶1活力分别上升58.05%、49.60%(P<0.01)。结论:DNJ可能通过降低肥胖小鼠炎症程度,改善FGF21与脂联素水平,进一步上调腺苷酸活化蛋白激酶α1表达,促进肥胖小鼠肝脏线粒体生物合成与自噬,同时使线粒体脂肪酸氧化限速酶肉碱棕榈酰转移酶1活性上升,促进脂肪酸分解,达到降脂的目的。Mitochondria play an important role in regulating lipid metabolism as an important place for energy metabolism.This study investigated the effect of 1-deoxynojirimycin(DNJ)on mitochondrial synthesis and mitophagy in the hepatocytes of obese mice.An obese mouse model was established by feeding Kunming a high-fat diet,and then the obese mice were administered with DNJ at doses of 8.0,4.0 and 2.0 mg/(kg mb·d)for 45 days.At the end of this period,serum and liver parameters were determined.The results showed that compared with the obese control group,high-dose DNJ could delay body mass gain,mitigate inflammation,significantly increase serum adiponectin by 43.19%and 29.58%(P<0.01)in female and male mice.In addition,it could increase fibroblast growth factor 21(FGF21)in female mice by 37.03%(P<0.01),and improve FGF21 resistance in male mice.Also it could upregulate the mRNA expression of adenosine 5’-monophosphate(AMP)-activated protein kinase(AMPK)α1 as well as the mRNA expression of peroxisome proliferator activated receptorγcoactivator-1α,nuclear respiratory factor 1 and unc-51 like kinase 1,all related to mitochondrial biosynthesis,to increase the corresponding protein levels by 28.27%and 43.99%(P<0.01),50.25%and 40.26%(P<0.01),and 19.24%and 22.76%(P<0.05)in female and male mice,and increase carnitine palmitoyltransferase1 activity by 58.05%and 49.60%(P<0.05)in female and male mice,respectively.Conclusion:DNJ can control body mass by reducing inflammation,improving FGF21 and adiponectin levels,upregulating the mRNA expression of AMPKα1 to promote mitochondrial biosynthesis and autophagy and simultaneously activating the fatty acid oxidation rate-limiting enzyme,carnitine palmitoyltransferase 1 to promote fatty acid breakdown.

关 键 词：1-脱氧野尻霉素 线粒体生物合成 线粒体自噬 肥胖 

分 类 号：TS201.4[轻工技术与工程—食品科学]