Relationship of mitochondrial fusion/fission genes with dihydromyricetin inhibiting liver fat accumulation in high-fat fed mice

Xin MA; Ka CHEN; Li RAN; Jundong ZHU; Mantian MI

doi:10.16016/j.1000-5404.201709101

您当前的位置：

首页 >

文章列表页 >

Relationship of mitochondrial fusion/fission genes with dihydromyricetin inhibiting liver fat accumulation in high-fat fed mice

Basic Medicine | 更新时间：2026-01-09

- Relationship of mitochondrial fusion/fission genes with dihydromyricetin inhibiting liver fat accumulation in high-fat fed mice
- Journal of Third Military Medical University Vol. 40, Issue 1, Pages: 17-22(2018)
- 作者机构：
  
  1.400038 重庆, 第三军医大学军事预防医学院营养与食品安全研究中心, 重庆市营养与食品安全重点实验室, 重庆市医学营养研究中心
  2.610083 成都, 中国人民解放军成都总医院康复医学科
- 作者简介：
- 基金信息：
  
  Supported by the General Program of National Natural Science Foundation of China(81372975)
- DOI：10.16016/j.1000-5404.201709101
  CLC： R-332;R575.5;R977.6
- Received：13 September 2017，
  
  Revised：2017-10-17，
  
  Published：15 January 2018
- 稿件说明：
移动端阅览
Xin MA, Ka CHEN, Li RAN, et al. Relationship of mitochondrial fusion/fission genes with dihydromyricetin inhibiting liver fat accumulation in high-fat fed mice[J]. Journal of Third Military Medical University, 2018, 40(1): 17-22.
DOI：

Xin MA, Ka CHEN, Li RAN, et al. Relationship of mitochondrial fusion/fission genes with dihydromyricetin inhibiting liver fat accumulation in high-fat fed mice[J]. Journal of Third Military Medical University, 2018, 40(1): 17-22. DOI： 10.16016/j.1000-5404.201709101.

摘要

目的

探讨肝脏线粒体融裂相关基因表达变化在二氢杨梅素抑制高脂喂养小鼠肝脏脂肪蓄积中的可能作用。

方法

45只6周龄C57BL/6J雄性小鼠

按随机数表法分为普通饲料组(CON)

高脂饲料组(HFD)和高脂加二氢杨梅素组(HFD+DHM)

每组15只

干预12周。检测小鼠体质量、肝脏指数、血清生化指标; 分别采用HE染色和油红O染色观察肝细胞脂肪变性和脂滴数量与形态。使用增强型ATP试剂盒检测肝脏ATP含量; 采用荧光定量PCR和Western blot分别检测肝脏线粒体融合与分裂相关基因[动力相关蛋白1(dynamin-related protein 1

Drp1)、分裂蛋白1(fission 1

Fis1)、融合蛋白2(mitofusion 2

Mfn2)、视神经萎缩蛋白1(optic atrophy1

Opa1)]的mRNA及蛋白表达。

结果

与CON组相比

HFD组小鼠体质量、肝脏指数、空腹血糖、空腹胰岛素水平、甘油三酯、总胆固醇、低密度胆固醇明显增高(

0.05)

肝脏ATP含量显著降低(

0.05)

HE染色见明显的肝内脂肪空泡和肝细胞气球样变

油红O

染色见大量的脂滴蓄积

肝脏组织Fis1、Drp1 mRNA和蛋白表达显著增高(

0.05)

而Mfn2、Opa1明显降低(

0.05)。二氢杨梅素干预显著抑制高脂喂养诱导的肝脏指数、空腹血糖、空腹胰岛素和血甘油三酯的升高

肝脏脂肪蓄积以及肝脏ATP含量的降低

并且明显拮抗高脂诱导的线粒体分裂与融合基因mRNA和蛋白的表达水平变化。

结论

二氢杨梅素可明显改善高脂喂养小鼠肝脏的脂肪蓄积

该效应可能与其调节肝脏线粒体的融合与分裂有关。

Abstract

Objective

To investigate the role of the hepatic mitochondrial fusion/fission-related genes in the dihydromyricetin (DHM)-induced inhibition of liver fat accumulation in mice after high-fat diet (HFD).

Methods

Forty-five male C57BL/6J mice (6 weeks old) were randomly divided into control group (CON)

HFD group (HFD) and HFD with DHM treatment (HFD+DHM)

with 15 mice per group.After 12 weeks

the body weight

hepatic index and serum biochemical indexes were detected.HE and oil red O staining were applied to observe the changes of hepatic steatosis and lipid droplets accumulation.The ATP production was measured by an enhanced ATP detecting kit.The mRNA and protein levels of mitochondrial fusion/fission genes

fission 1 (Fis1)

dynamin-related protein 1 (Drp1)

mitofusion 2 (Mfn2) and optic atrophy1 (Opa1) were determined by PCR and Western blotting.

Results

HFD significantly increased body weight

hepatic index

fasting glucose

fasting insulin

triglyceride

total cholesterol and low density lipoprotein (

0.05)

while decreased the ATP production(

0.05).HE staining displayed notable intrahepatic fat vacuoles and hepatocyte balloon-like changes in the liver of HFD mice.And oil red O staining showed more fat droplets in HFD mice.The mRNA and protein levels of hepatic Fis1and Drp1 were significantly increased (

0.05)

while those of Mfn2 and Opa1 were dominantly decreased in HFD group (

0.05).However

DHM treatment could significantly reverse all above

changes induced by HFD(

0.05).

Conclusion

DHM attenuates lipid accumulation in the HFD mice

which may be related to its regulation on mitochondrial fusion/fission functions.

关键词

Keywords

references

GALLOWAY C A, LEE H, BROOKES P S, et al .Decreasing mitochondrial fission alleviates hepatic steatosis in a murine model of nonalcoholic fatty liver disease[J ] .Am J Physiol Gastrointest Liver Physiol, 2014, 307(6):G632-G641.DOI:10.1152/ajpgi.00182.2014.

SCOTT I, YOULE R J.Mitochondrial fission and fusion[J].Essays Biochem, 2010, 47:85-98.DOI:10.1042/bse0470085.

SERVIDDIO G, BELLANTI F, VENDEMIALE G, et al .Mitochondrial dysfunction in nonalcoholic steatohepatitis[J ] .Expert Rev Gastroenterol Hepatol, 2011, 5(2):233-244.DOI:10.1586/egh.11.11.

MISHRA P.Interfaces between mitochondrial dynamics and disease[J].Cell Calcium, 2016, 60(3):190-198.DOI:10.1016/j.ceca.2016.05.004.

CHEN S, ZHAO X, WAN J, et al .Dihydromyricetin improves glucose and lipid metabolism and exerts anti-inflammatory effects in nonalcoholic fatty liver disease:A randomized controlled trial[J ] .Pharmacol Res, 2015, 99:74-81.DOI:10.1016/j.phrs.2015.05.009.

李成凤, 曾祥龙, 黄娟, 等.二氢杨梅素上调SIRT1信号通路改善HepG2细胞甘油三酯蓄积[J].第三军医大学学报, 2016, 38(5):443-448.DOI:10.16016/j.1000-5404.201509009.

LI C F, ZENG X L, Huang Juan, et al .Dihydromyricetin improves triglyceride accumulation in hepg2 cells by regulating SIRT1 signaling pathway[J ] .J Third Mil Med Univ, 2016, 38(5):443-448.DOI:10.16016/j.1000-5404.201509009.

HORBAY R, BILYY R.Mitochondrial dynamics during cell cycling[J].Apoptosis, 2016, 21(12):1327-1335.DOI:10.1007/s10495-016-1295-5.

BASARANOGLU M, KAYACETIN S, YILMAZ N, et al .Understanding mechanisms of the pathogenesis of nonalcoholic fatty liver disease[J ] .World J Gastroenterol, 2010, 16(18):2223-2226.

IBRAHIM MA, KELLENI M, GEDDAWY A.Nonalcoholic fatty liver disease:current and potential therapies[J].LifeSci, 2013, 92(2):114-118.DOI:10.1016/j.lfs.2012.11.004.

NASSIR F, IBDAH J A.Role of mitochondria in alcoholic liver disease[J].World J Gastroenterol, 2014, 20(9):2136-2142.DOI:10.3748/wjg.v20.i9.2136.

Basaranoglu M, Basaranoglu G, Sent rk H.From fatty liver to fibrosis:a tale of "second hit"[J].World J Gastroenterol, 2013, 19(8):1158-1165.DOI:10.3748/wjg.v19.i8.1158.

李香云, 余剑波.线粒体的融合、分裂与炎症反应研究进展[J].中国病理生理杂志, 2016, 32(12):2295-2299.DOI:10.3969/j.issn.1000-4718.2016.12.030.

LI X Y, YU J B.Progress in mitochondrial fusion, fission and inflammatory response[J].Chin J Pathophysiol, 2016, 32(12):2295-2299.DOI:10.3969/j.issn.1000-4718.2016.12.030.

BEGRICHE K, MASSART J, ROBIN M A, et al .Mitochondrial adaptations and dysfunctions in nonalcoholic fatty liver disease[J ] .Hepatology, 2013, 58(4):1497-1507.DOI:10.1002/hep.26226.

SPAHIS S, DELVIN E, BORYS J M, et al .Oxidative stress as a critical factor in nonalcoholic fatty liver disease pathogenesis[J ] .Antioxid Redox Signal, 2017, 26(10):519-541.DOI:10.1089/ars.2016.6776.

HOU X, TONG Q, WANG W, et al .Dihydromyricetin protects endothelial cells from hydrogen peroxide-induced oxidative stress damage by regulating mitochondrial pathways[J ] .Life Sci, 2015, 130:38-46.DOI:10.1016/j.lfs.2015.03.007.

MICHALSKA B, DUSZYŃSKI J, SZYMAŃSKI J.Mechanism of mitochondrial fission-structure and function of Drp1 protein[J].Postepy Biochem, 2016, 62(2):127-137.

KAWALEC M, BERESEWICZ M, ZABŁOCKI K, et al .Mitofusin 2 and mitochondrial dynamics in norm and pathology[J ] .Postepy Biochem, 2016, 62(2):149-157.

PERNAS L, SCORRANO L.Mito-morphosis:mitochondrial fusion, fission, and cristae remodeling as key mediators of cellular function[J].Annu Rev Physiol, 2016, 78:505-531.DOI:10.1146/annurev-physiol-021115-105011.

GRATTAGLIANO I, DE BARI O, BERNARDO T C, et al .Role of mitochondria in nonalcoholic fatty liver disease—from origin to propagation[J ] .Clin Biochem, 2012, 45(9):610-618.DOI:10.1016/j.clinbiochem.2012.03.024.

郑靖宇, 吴欢, 汤雯, 等.Drp1和Mfn2在棕榈酸诱导大鼠肝细胞损伤中的作用机制及姜黄素衍生物L6H4的干预作用[J].温州医科大学学报, 2016, 46(7):469-475, 481.DOI:10.3969/j.issn.2095-9400.2016.07.001.

ZHENG J Y, WU H, TANG W, et al .Roles of drp1 and mfn2 in palmitate induced rat hepatocyte injury and the effects of curcumin derivative l6h4 on it[J ] .J Wenzhou Med Univ, 2016, 46(7):469-475, 481.DOI:10.3969/j.issn.2095-9400.2016.07.001.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Dihydromyricetin improves rhythm disorder in expression of liver circadian clock genes in nonalcoholic fatty liver mice

p300 promotes hepatic lipid accumulation in dyslipidemia by regulating SREBP-1c acetylation

Estimated glucose disposal rate as a practical tool for non-alcoholic fatty liver disease identification: A NHANES-based cross-sectional study uncovering its protective threshold

Screening and validation of key molecular targets for dihydromyricetin in ameliorating diabetic nephropathy

Dihydromyricetin ameliorates vascular endothelial damage by inhibiting NLRP3 inflammasome activity through Sirtuin 3

Related Author

马鑫

时皎皎

陈卡

易龙

朱俊东

糜漫天

NUHU Abdul-Rauf Nyewneh

LI Xiaoli

Related Institution

达州市中西医结合医院药学科

陆军军医大学大坪医院药剂科

Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology，Chongqing；⁴Department of Pharmacy，Daping Hospital，Army Medical University （Third Military Medical University）， Chongqing； ⁵Department of Pharmacy，Dazhou Hospital of Integrated Traditional Chinese and Western Medicine

Department of Gastrointestinal Surgery，the First Affiliated Hospital of Chongqing Medical University

College of Pharmacy，Chongqing Medical University

⁰