ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Issue 9
Sep.  2016
Turn off MathJax
Article Contents

Effect of blueberry and probiotics on expression of PNPLA3 and SREBP-1c in rats with nonalcoholic fatty liver disease

DOI: 10.3969/j.issn.1001-5256.2016.09.031
Research funding:


  • Published Date: 2016-09-20
  • Objective To investigate the expression of patatin- like phospholipase domain- containing protein 3( PNPLA3) and sterol regulatory element- binding protein- 1c( SREBP- 1c) in the rat model of nonalcoholic fatty liver disease( NAFLD) treated by blueberry combined with probiotics,as well as its mechanism of action in NAFLD. Methods A total of 36 clean Sprague- Dawley rats were divided into normal group( NG),model group( MG),spontaneous recovery group( SRG),blueberry group( BG),probiotics group( PG),and blueberry- probiotics group( BPG). Tissue sections were prepared after the experiment ended to observe serological and histological changes and measure the mRNA and protein expression of PNPLA3 and SREBP- 1c. A one- way analysis of variance was used for comparison between multiple groups; the SNK- q test was used for data with homogeneity of variance,and the Tamhane's- T2 test was used for data with heterogeneity of variance. Results The six groups showed significant differences in liver index,serum alanine aminotransferase,total cholesterol,triglyceride,low- density lipoprotein,and high- density lipoprotein( F = 384. 908,188. 554,75. 523,94. 667,95. 235,and132. 586,all P < 0. 01). The NAFLD activity score also showed a significant difference between the six groups( F = 71. 896,P < 0. 01),and BPG showed a significantly greater reduction in the NAFLD activity score than MG,SRG,BG,and PG( all P < 0. 01). The six groups showed significant differences in the positive rates of PNPLA3 and SREBP- 1c in liver tissue( F = 175. 527 and 110. 504,both P < 0. 01),and BPG showed a significantly greater reduction in the positive rates of PNPLA3 and SREBP- 1C than MG,SRG,BG,and PG( all P <0. 01). The mRNA and protein expression of PNPLA3 and SREBP- 1c showed a significantly difference between the six groups.( F =375. 822,410. 379,288. 940,116. 054,all P < 0. 01). BPG showed significant reductions in the mRNA expression of PNPLA3 and SREBP- 1c compared with MG,SRG,BG,and PG( all P < 0. 01). Conclusion Blueberry combined with probiotics can effectively improve the structure of pathological tissues in NAFLD and reduce hepatocyte fatty degeneration. Its mechanism may be that the combination of blueberry and probiotics can reduce inflammation induced by inflammatory factors and downregulate the expression of SREBP- 1c,and thus weaken PNPLA3 gene transcription,enhance cholesterol metabolism,and reduce lipid deposition. Therefore,it can be applied as adjuvant therapy for NAFLD.


  • loading
  • [1]LOOMBA R,SANYAL A.The global NAFLD epidemic[J].Nat Rev Gastroenterol Hepatol,2013,10(11):686-690.
    [2]MILIC S,STIMAC D.Nonalcoholic fatty liver disease/steatohepatitis:epidemiology,pathogenesis,clinical presentation and treatment[J].Dig Dis,2012,30(2):158-162.
    [3]PINGITORE P,PIRAZZI C,MANCINA R,et al.Recombinant PNPLA3 protein shows triglyceride hydrolase activity and its I148M mutation results in loss of function[J].Biochim Biophys Acta,2014,1841(11):574-580.
    [4] DUBUQUOY C,ROBICHON C,LASNIER F,et al.Distinct regulation of adiponutrin/PNPLA3 gene expression by the transcription factors ChREBP and SREBP1c in mouse and human hepatocytes[J].J Hepatol,2011,55(10):145-153.
    [5]CHALASANI N,YOUNOSSI Z,LAVINE J,et al.The diagnosis and management of non-alcoholic fatty liver disease:practice guideline by the American Association for the Study of Liver Diseases,American College of Gastroenterology,and the American Gastroenterological Association[J].Hepatology,2012,55(6):2005-2023.
    [6]WONG V,WON G,CHIM A,et al.Treatment of nonalcoholic steatohepatitis with probiotics.A proof-of-concept study[J].Ann Hepatol,2013,12(2):256-262.
    [7]ESLAMPARAST T,POUSTCHI H,ZAMANI F,et al.Synbiotic supplementation in nonalcoholic fatty liver disease:a randomized,double-blind,placebo-controlled pilot study[J].Am J Clin Nutr,2014,99(3):535-542.
    [8]REN T,HUANG C,CHENG M.Dietary blueberry and bifidobacteria attenuate nonalcoholic fatty liver disease in rats by affecting SIRT1-mediated signaling pathway[J].Oxid Med Cell Longev,2014,2014(10):465059.
    [9]CANO A,CIAFFONI F,SAFWAT GM,et al.Hepatic VLDL assembly is disturbed in a rat model of nonalcoholic fatty liver disease:is there a role for dietary coenzyme Q[J].J Appl Physiol,2009,107(3):707-717.
    [10]WEN GQ,NIE F,FANG PW.Comparative analysis of physicochemical component content in blueberry fruit and their function evaluation[J].Acta Agricult Jiangxi,2011,24(1):117-119.(in Chinese)文光琴,聂飞,方品武.蓝莓果实理化成分含量比较分析与功能评价[J].江西农业学报,2011,24(1):117-119.
    [11]WANG Y,CHENG M,ZHANG B,et al.Dietary supplementation of blueberry juice enhances hepatic expression of metallothionein and attenuates liver fibrosis in rats[J].PLo S One,2013,8(3):e58659.
    [12]OSMAN N,ADAWI D,AHRNES,et al.Endotoxin-and D-galactosamine-induced liver injury improved by the administration of Lactobacillus,Bifidobacterium and blueberry[J].Dig Liver Dis,2007,39(9):849-856.
    [13]FARRELL G,CHITTURI S,LAU G,et al.Guidelines for the assessment and management of non-alcoholic fatty liver disease in the Asia-Pacific region:executive summary[J].J Gastroenterol Hepatol,2007,22(5):775-777.
    [14]ZENG M,FAN J,LU L,et al.Guidelines for the diagnosis and treatment of nonalcoholic fatty liver diseases[J].J Dig Dis,2008,9(6):108-112.
    [15]DUBUQUOY C,ROBICHON C,LASNIER F,et al.Distinct regulation of adiponutrin/PNPLA3 gene expression by the transcription factors ChREBP and SREBP1c in mouse and human hepatocytes[J].J Hepatol,2011,55(11):145-153.
    [16]SHEN J,WONG G,CHAN H,et al.PNPLA3 gene polymorphism accounts for fatty liver in community subjects without metabolic syndrome[J].Aliment Pharmacol Ther,2014,39(5):532-539.
    [17]ERIKS S,SOUMIK B,JOHN L,et al.Pnpla3I148M knockin mice accumulate PNPLA3 on lipid droplets and develop hepatic steatosis[J].Hepatology,2015,61(1):108-118.
    [18]KENTARO O,JUNJI S,TOMOKO L,et al.Influence of the PNPLA3 rs738409 polymorphism on non-alcoholic fatty liver disease and renal function among normal weight subjects[J].PLo S One,2015,10(7):e0132640.
    [19]QIAN A,LIANG J,KE Y,et al.Mouse patatin-like phospholipase domain-containing 3 influences systemic lipid and glucose homeostasis[J].Hepatology,2011,54(2):509-521.
    [20]FERNANDES I,MARQUES F,FREITAS V,et al.Antioxidant and anti-proliferative properties of methylated metabolites of anthocyanins[J].Food Chem,2013,141(3):2923-2933.
    [21]VENDRAME S,DAUGHERTY A,KRISTO A,et al.Wild blueberry(vaccinium angustifolium)consumption improves inflammatory status in the obese Zucker rat model of the metabolic syndrome[J].J Nutr Biochem,2013,24(8):1508-1512.
    [22]ZHAO XK,WU RM,YAO YM,et al.Effects of blueberry on the expression of TNF-α-R1 and SREBP-1c in acute alcoholic fatty liver[J].J Chongqing Med Univ,2015,40(3):354-357.(in Chinese)赵雪珂,吴荣敏,姚玉梅,等.蓝莓对小鼠急性酒精性脂肪肝TNF-α-R1和SREBP-1c影响的初步研究[J].重庆医科大学学报,2015,40(3):354-357.
    [23]LIU YW,ZHOU F,HAO JX,et al.Supplement of blueberry juice and its extracts to improve the growth of Lactobacillus acidophilus NCFM as probiotic adjunct[J].China Dairy Ind,2013,41(2):13-16.(in Chinese)刘奕炜,周方,郝建新,等.蓝莓汁及其提取物对嗜酸乳杆菌NCFM体外生长的影响[J].中国乳品工业,2013,41(2):13-16.
    [24]BRANNING C,HAKANSSON A,AHRNE S,et al.Blueberry husks and multi-strain probiotics affect clolnic fermentation in rats[J].Br J Nutr,2009,101(6):859-870.
    [25]ASA H,CAMILLA B,GORAN M,et al.Blueberry Husks and probiotics attenuate colorectal inflammation and oncogenesis,and liver injuries in rats exposed to cycling DSS-treatment[J].PLo S One,2012,7(3):e33510.
    [26]XU Q,LIU HX,XU F,et al.SREBP-1c activates PNPLA3 gene transcription[C]//Proceedings of the 16th National Academic Conference of Chinese Society of Diabetes,Chinese Medical Association,2012.(in Chinese)许晴,刘宏霞,徐芬,等.SREBP-1c激活PNPLA3基因转录[C]//中华医学会糖尿病学分会第十六次全国学术会议论文集,2012.
  • 加载中


    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Article Metrics

    Article views (2115) PDF downloads(456) Cited by()
    Proportional views


    DownLoad:  Full-Size Img  PowerPoint