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The Combination of Blueberry Juice and Probiotics Ameliorate Non-Alcoholic Steatohepatitis (NASH) by Affecting SREBP-1c/PNPLA-3 Pathway via PPAR-α.

Abstract

Nonalcoholic steatohepatitis (NASH) is liver inflammation and a major threat to public health. Several pharmaceutical agents have been used for NASH therapy but their high-rate side effects limit the use. Blueberry juice and probiotics (BP) have anti-inflammation and antibacterial properties, and may be potential candidates for NASH therapy. To understand the molecular mechanism, Sprague Dawley rats were used to create NASH models and received different treatments. Liver tissues were examined using HE (hematoxylin and eosin) and ORO (Oil Red O) stain, and serum biochemical indices were measured. The levels of peroxisome proliferators-activated receptor (PPAR)-α, sterol regulatory element binding protein-1c (SREBP-1c), Patatin-like phospholipase domain-containing protein 3 (PNPLA-3), inflammatory cytokines and apoptosis biomarkers in liver tissues were measured by qRT-PCR and Western blot. HE and ORO analysis indicated that the hepatocytes were seriously damaged with more and larger lipid droplets in NASH models while BP reduced the number and size of lipid droplets (p < 0.05). Meanwhile, BP increased the levels of SOD (superoxide dismutase), GSH (reduced glutathione) and HDL-C (high-density lipoprotein cholesterol), and reduced the levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), TG (triglycerides), LDL-C (low-density lipoprotein cholesterol) and MDA (malondialdehyde) in NASH models (p < 0.05). BP increased the level of PPAR-α (Peroxisome proliferator-activated receptor α), and reduced the levels of SREBP-1c (sterol regulatory element binding protein-1c) and PNPLA-3 (Patatin-like phospholipase domain-containing protein 3) (p < 0.05). BP reduced hepatic inflammation and apoptosis by affecting IL-6 (interleukin 6), TNF-α (Tumor necrosis factor α), caspase-3 and Bcl-2 in NASH models. Furthermore, PPAR-α inhibitor increased the level of SREBP-1c and PNPLA-3. Therefore, BP prevents NASH progression by affecting SREBP-1c/PNPLA-3 pathway via PPAR-α.

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  • Authors+Show Affiliations

    ,

    Biochemistry Department, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, China. tingting1@163.com.

    ,

    Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, China. juanjuan2@163.com. Baiyun Hospital, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, China. juanjuan2@163.com.

    ,

    Baiyun Hospital, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, China. zhulili1@163.com.

    Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, China. minglianggy@163.com.

    Source

    Nutrients 9:3 2017 Feb 27 pg

    MeSH

    Alanine Transaminase
    Animals
    Apoptosis
    Aspartate Aminotransferases
    Bifidobacterium animalis
    Blueberry Plants
    Caspase 3
    Cholesterol
    Disease Models, Animal
    Fruit
    Fruit and Vegetable Juices
    Hep G2 Cells
    Hepatocytes
    Humans
    Interleukin-6
    Lactobacillus delbrueckii
    Lipid Metabolism
    Male
    Malondialdehyde
    Membrane Proteins
    Non-alcoholic Fatty Liver Disease
    PPAR alpha
    Phospholipases A2
    Probiotics
    Proto-Oncogene Proteins c-bcl-2
    Rats
    Rats, Sprague-Dawley
    Signal Transduction
    Sterol Regulatory Element Binding Protein 1
    Streptococcus thermophilus
    Triglycerides
    Tumor Necrosis Factor-alpha

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    28264426

    Citation

    Ren, Tingting, et al. "The Combination of Blueberry Juice and Probiotics Ameliorate Non-Alcoholic Steatohepatitis (NASH) By Affecting SREBP-1c/PNPLA-3 Pathway Via PPAR-α." Nutrients, vol. 9, no. 3, 2017.
    Ren T, Zhu J, Zhu L, et al. The Combination of Blueberry Juice and Probiotics Ameliorate Non-Alcoholic Steatohepatitis (NASH) by Affecting SREBP-1c/PNPLA-3 Pathway via PPAR-α. Nutrients. 2017;9(3).
    Ren, T., Zhu, J., Zhu, L., & Cheng, M. (2017). The Combination of Blueberry Juice and Probiotics Ameliorate Non-Alcoholic Steatohepatitis (NASH) by Affecting SREBP-1c/PNPLA-3 Pathway via PPAR-α. Nutrients, 9(3), doi:10.3390/nu9030198.
    Ren T, et al. The Combination of Blueberry Juice and Probiotics Ameliorate Non-Alcoholic Steatohepatitis (NASH) By Affecting SREBP-1c/PNPLA-3 Pathway Via PPAR-α. Nutrients. 2017 Feb 27;9(3) PubMed PMID: 28264426.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - The Combination of Blueberry Juice and Probiotics Ameliorate Non-Alcoholic Steatohepatitis (NASH) by Affecting SREBP-1c/PNPLA-3 Pathway via PPAR-α. AU - Ren,Tingting, AU - Zhu,Juanjuan, AU - Zhu,Lili, AU - Cheng,Mingliang, Y1 - 2017/02/27/ PY - 2016/12/17/received PY - 2017/02/14/revised PY - 2017/02/21/accepted PY - 2017/3/8/entrez PY - 2017/3/8/pubmed PY - 2017/8/18/medline KW - Patatin-like phospholipase domain-containing protein 3 KW - Peroxisome proliferator-activated receptor α KW - Sterol regulatory element-binding transcription factor 1c KW - anti-oxidant KW - apoptosis KW - biochemical indices KW - blueberry juices KW - non-alcoholic steatohepatitis KW - probiotics JF - Nutrients JO - Nutrients VL - 9 IS - 3 N2 - Nonalcoholic steatohepatitis (NASH) is liver inflammation and a major threat to public health. Several pharmaceutical agents have been used for NASH therapy but their high-rate side effects limit the use. Blueberry juice and probiotics (BP) have anti-inflammation and antibacterial properties, and may be potential candidates for NASH therapy. To understand the molecular mechanism, Sprague Dawley rats were used to create NASH models and received different treatments. Liver tissues were examined using HE (hematoxylin and eosin) and ORO (Oil Red O) stain, and serum biochemical indices were measured. The levels of peroxisome proliferators-activated receptor (PPAR)-α, sterol regulatory element binding protein-1c (SREBP-1c), Patatin-like phospholipase domain-containing protein 3 (PNPLA-3), inflammatory cytokines and apoptosis biomarkers in liver tissues were measured by qRT-PCR and Western blot. HE and ORO analysis indicated that the hepatocytes were seriously damaged with more and larger lipid droplets in NASH models while BP reduced the number and size of lipid droplets (p < 0.05). Meanwhile, BP increased the levels of SOD (superoxide dismutase), GSH (reduced glutathione) and HDL-C (high-density lipoprotein cholesterol), and reduced the levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), TG (triglycerides), LDL-C (low-density lipoprotein cholesterol) and MDA (malondialdehyde) in NASH models (p < 0.05). BP increased the level of PPAR-α (Peroxisome proliferator-activated receptor α), and reduced the levels of SREBP-1c (sterol regulatory element binding protein-1c) and PNPLA-3 (Patatin-like phospholipase domain-containing protein 3) (p < 0.05). BP reduced hepatic inflammation and apoptosis by affecting IL-6 (interleukin 6), TNF-α (Tumor necrosis factor α), caspase-3 and Bcl-2 in NASH models. Furthermore, PPAR-α inhibitor increased the level of SREBP-1c and PNPLA-3. Therefore, BP prevents NASH progression by affecting SREBP-1c/PNPLA-3 pathway via PPAR-α. SN - 2072-6643 UR - https://www.unboundmedicine.com/medline/citation/28264426/The_Combination_of_Blueberry_Juice_and_Probiotics_Ameliorate_Non_Alcoholic_Steatohepatitis__NASH__by_Affecting_SREBP_1c/PNPLA_3_Pathway_via_PPAR_α_ L2 - http://www.mdpi.com/resolver?pii=nu9030198 DB - PRIME DP - Unbound Medicine ER -