中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

Effect of hepatocyte fatty degeneration induced by free fatty acid on macrophage polarization

DOI: 10.3969/j.issn.1001-5256.2021.02.027
  • Received Date: 2020-08-27
  • Accepted Date: 2020-10-21
  • Published Date: 2021-02-20
  •   Objective  To investigate the effect of hepatocyte fatty degeneration induced by free fatty acid on macrophage polarization and the possible mechanism.  Methods  Primary hepatocytes of C57BL/6 mice were isolated by in situ collagenase perfusion, and then the hepatocytes were divided into control (NC) group and mixed free fatty acid (FFA) treatment group. A conditioned medium (CM) was prepared for hepatocytes and was used for the intervention of RAW264.7 macrophages. Oil red O staining was used to observe lipid deposition in hepatocytes; real-time PCR was used to measure the mRNA expression of lipid metabolism genes and macrophage M1/M2 polarization markers; ELISA was used to measure the levels of cytokines in supernatant; Western blot was used to measure the expression of proteins involved in the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway in macrophages. The independent samples t-test was used for comparison between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the Tukey test was used for further comparison between two groups.  Results  Compared with the NC group, the FFA treatment group had the deposition of massive lipid droplets in hepatocytes and significant increases in triglyceride and total cholesterol (t=15.65 and 3.49, both P < 0.05). Besides, FFA significantly increased the mRNA expression of the lipid synthesis genes SREBP1C and FASN (t=2.89 and 2.82, both P < 0.05) and reduced the mRNA expression of the lipid decomposition genes ACOX1 and CPT1A (t=14.30 and 3.36, both P < 0.05) in hepatocytes. FFA also induced significant increases in the levels of the inflammatory cytokines interleukin-6 (IL-6), interleukin-1β, and tumor necrosis factor-α (TNF-α) in supernatant (all P < 0.05). Compared with the CM-NC group, the CM-FFA group had significant increases in the mRNA expression of the M1 phenotype markers iNOS2, TNF-α, and IL-6 (all P < 0.05) and a significant reduction in the mRNA expression of the M2 phenotype marker interleukin-10 (P < 0.05). Moreover, Western blot showed that CM-FFA significantly upregulated the protein expression of TLR4, p-NF-κBp65, and p-ⅠκBα in macrophages (t=2.88, 3.69, and 3.54, all P < 0.05).  Conclusion  FFA-induced hepatocyte fatty degeneration and inflammation can promote M1 macrophage polarization, thereby initiating and triggering the development and progression of nonalcoholic fatty liver disease.

     

  • [1]
    YOUNOSSI ZM. Non-alcoholic fatty liver disease - A global public health perspective[J]. J Hepatol, 2019, 70(3): 531-544. DOI: 10.1016/j.jhep.2018.10.033
    [2]
    TACKE F. Targeting hepatic macrophages to treat liver diseases[J]. J Hepatol, 2017, 66(6): 1300-1312. DOI: 10.1016/j.jhep.2017.02.026
    [3]
    WANG Q, XU QY, WU HM, et al. Effect of lipid-induced macrophage M1/M2 polarization on lipid metabolism in hepatocytes[J]. Chin J Hepatol, 2018, 26(4): 276-281. (in Chinese) DOI: 10.3760/cma.j.issn.1007-3418.2018.04.009

    王祺, 许钦瑜, 吴惠敏, 等.脂质诱导的巨噬细胞M1/M2型极化对肝细胞脂质代谢的影响[J].中华肝脏病杂志, 2018, 26(4): 276-281. DOI: 10.3760/cma.j.issn.1007-3418.2018.04.009
    [4]
    GÓMEZ-LECHÓN MJ, DONATO MT, MARTÍNEZ-ROMERO A, et al. A human hepatocellular in vitro model to investigate steatosis[J]. Chem Biol Interact, 2007, 165(2): 106-116. DOI: 10.1016/j.cbi.2006.11.004
    [5]
    XIAO WS, LE YY, ZENG SL, et al. Research advances in the pathogenesis of nonalcoholic fatty liver disease[J]. J Clin Hepatol, 2020, 36(8): 1874-1879. (in Chinese) DOI: 10.3969/j.issn.1001-5256.2020.08.043

    肖伟松, 乐滢玉, 曾胜澜, 等.非酒精性脂肪性肝病的发病机制研究进展[J].临床肝胆病杂志, 2020, 36(8): 1874-1879. DOI: 10.3969/j.issn.1001-5256.2020.08.043
    [6]
    HOLLAND WL, BIKMAN BT, WANG LP, et al. Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid-induced ceramide biosynthesis in mice[J]. J Clin Invest, 2011, 121(5): 1858-1870. DOI: 10.1172/JCI43378
    [7]
    KAZANKOV K, JØRGENSEN S, THOMSEN KL, et al. The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis[J]. Nat Rev Gastroenterol Hepatol, 2019, 16(3): 145-159. DOI: 10.1038/s41575-018-0082-x
    [8]
    TOSELLO-TRAMPONT AC, LANDES SG, NGUYEN V, et al. Kuppfer cells trigger nonalcoholic steatohepatitis development in diet-induced mouse model through tumor necrosis factor-α production[J]. J Biol Chem, 2012, 287(48): 40161-40172. DOI: 10.1074/jbc.M112.417014
    [9]
    WU HM, NI XX, XU QY, et al. Regulation of lipid-induced macrophage polarization through modulating peroxisome proliferator-activated receptor-gamma activity affects hepatic lipid metabolism via a Toll-like receptor 4/NF-κB signaling pathway[J]. J Gastroenterol Hepatol, 2020, 35(11): 1998-2008. DOI: 10.1111/jgh.15025
    [10]
    KOU XN, XIE XK, HAO MX, et al. Effects and mechanism of microRNA-140 inhibition on the development of non-alcoholic fatty liver disease in mice[J/CD]. Chin J Liver Dis (Electronic Version), 2020, 12(3): 34-40. (in Chinese)

    寇小妮, 解新科, 郝明霞, 等.微小RNA-140抑制对小鼠非酒精性脂肪性肝病进展的影响及机制[J/CD].中国肝脏病杂志(电子版), 2020, 12(3): 34-40.
    [11]
    ZHENG Y, WANG JR, LIU LL, et al. Molecular mechanism of the anti -liver fibrosis effect of curcumol: An analysis based on the TLR4 /NF-κB signaling pathway[J]. J Clin Hepatol, 2020, 36(7): 1508-1513. (in Chinese) DOI: 10.3969/j.issn.1001-5256.2020.07.013

    郑洋, 王嘉孺, 刘露露, 等.基于Toll样受体4 /核因子-κB信号通路研究莪术醇抗肝纤维化的分子机制[J].临床肝胆病杂志, 2020, 36(7): 1508-1513. DOI: 10.3969/j.issn.1001-5256.2020.07.013
    [12]
    ZHANG CH, LI Y, LI ZY, et al. Protective effect of procyanidine B1 on LPS-induced injury of mouse macrophages RAW264.7 and its mechanism[J]. J Jilin Univ(Med Edit), 2019, 45(6): 1243-1247. (in Chinese) http://www.cnki.com.cn/Article/CJFDTotal-BQEB201906008.htm

    张宸豪, 李瑶, 李正祎, 等.原花青素B1对LPS诱导小鼠巨噬细胞RAW264.7损伤的保护作用及其机制[J].吉林大学学报(医学版), 2019, 45(6): 1243-1247. http://www.cnki.com.cn/Article/CJFDTotal-BQEB201906008.htm
    [13]
    GORDON S, MARTINEZ F O. Alternative activation of macrophages: Mechanism and functions[J]. Immunity, 2010, 32(5): 593-604. DOI: 10.1016/j.immuni.2010.05.007
  • Relative Articles

    [1]Linqi HOU, Zhiyi WANG, Xin ZHAO, Jie ZHANG, Wenting MA, Xuling LIU, Wei ZHANG, Le TAO, Cheng LIU, Liu WU. Therapeutic effect of Xiayuxue decoction on a mouse model of nonalcoholic fatty liver disease induced by high-fat diet and its mechanism[J]. Journal of Clinical Hepatology, 2024, 40(4): 712-719. doi: 10.12449/JCH240412
    [2]Tianhui LIU. Role of organelle interaction in the development and progression of nonalcoholic fatty liver disease[J]. Journal of Clinical Hepatology, 2023, 39(1): 181-187. doi: 10.3969/j.issn.1001-5256.2023.01.028
    [3]Jingya YIN, Bingqing YANG, Yue LI. Role of pyroptosis in nonalcoholic fatty liver disease[J]. Journal of Clinical Hepatology, 2023, 39(1): 175-180. doi: 10.3969/j.issn.1001-5256.2023.01.027
    [4]Yuesheng LIAO, Lili BAI. Role of exercise-induced autophagy in prevention and treatment of nonalcoholic fatty liver disease[J]. Journal of Clinical Hepatology, 2022, 38(5): 1156-1160. doi: 10.3969/j.issn.1001-5256.2022.05.038
    [5]Xuelian GU, Junfeng LI, Xiaorong MAO. Research advances in nonalcoholic fatty liver disease-related hepatocellular carcinoma[J]. Journal of Clinical Hepatology, 2022, 38(1): 196-200. doi: 10.3969/j.issn.1001-5256.2022.01.034
    [6]Qin LIU, Qiang ZHANG, Fangxiong WU, Rong YAN, Rong LI, Jia WANG, Chunyan NIU. Effect of amitriptyline on lipid deposition and biochemical metabolism in a cell model of nonalcoholic fatty liver disease[J]. Journal of Clinical Hepatology, 2021, 37(1): 99-104. doi: 10.3969/j.issn.1001-5256.2021.01.020
    [7]Jinxia ZHU, Guangwei LIU, Peiwei YANG. Influence of circadian rhythm disorder on nonalcoholic fatty liver disease and related hepatocellular carcinoma[J]. Journal of Clinical Hepatology, 2021, 37(10): 2469-2473. doi: 10.3969/j.issn.1001-5256.2021.10.045
    [8]Leigang JIN, Leiluo GENG, Aimin XU. Current status and perspectives of fibroblast growth factor 21 in nonalcoholic fatty liver disease[J]. Journal of Clinical Hepatology, 2021, 37(6): 1262-1267. doi: 10.3969/j.issn.1001-5256.2021.06.006
    [9]Juan WANG, Yingchun WANG, Chunyu WANG. Association between monocyte-to-high-density lipoprotein cholesterol ratio and nonalcoholic fatty liver disease[J]. Journal of Clinical Hepatology, 2021, 37(5): 1137-1141. doi: 10.3969/j.issn.1001-5256.2021.05.031
    [10]Shiyan YAN, Jiangao FAN. Diagnosis and treatment of hepatocellular carcinoma associated with nonalcoholic fatty liver disease[J]. Journal of Clinical Hepatology, 2021, 37(8): 1748-1752. doi: 10.3969/j.issn.1001-5256.2021.08.002
    [11]Yalan LEI, Jian BI, Jingwei MAO. Impact of nonalcoholic fatty liver disease on intestinal immune cells[J]. Journal of Clinical Hepatology, 2021, 37(11): 2667-2671. doi: 10.3969/j.issn.1001-5256.2021.11.039
    [12]YANG Jing, GAO Hong, ZHAO YaoWei, WANG Rui. Role of liver sinusoidal endothelial cells in the pathogenesis of nonalcoholic fatty liver disease[J]. Journal of Clinical Hepatology, 2020, 36(11): 2601-2605. doi: 10.3969/j.issn.1001-5256.2020.11.046
    [13]Zhang YongChao, Li Wei. Association between diabetes and nonalcoholic fatty liver disease-related hepatocellular carcinoma[J]. Journal of Clinical Hepatology, 2020, 36(10): 2329-2332. doi: 10.3969/j.issn.1001-5256.2020.10.037
    [14]Jiang Zhao, Ruan Bo. The role of liver sinusoidal endothelial cells in the progression of nonalcoholic fatty liver disease[J]. Journal of Clinical Hepatology, 2020, 36(3): 684-686. doi: 10.3969/j.issn.1001-5256.2020.03.047
    [15]Luo Yan, Shi JunPing. Research advances in the pathogenesis of nonalcoholic fatty liver disease-related hepatocellular carcinoma[J]. Journal of Clinical Hepatology, 2020, 36(6): 1217-1220. doi: 10.3969/j.issn.1001-5256.2020.06.005
    [16]Niu ChunYan, Zhao XiangYang. Hepatic macrophage-targeted therapy for fatty liver disease: Opportunities and challenges[J]. Journal of Clinical Hepatology, 2020, 36(6): 1393-1397. doi: 10.3969/j.issn.1001-5256.2020.06.045
    [17]Luo YuXin, Guo JinBo, Zhang XiaoLan. Research advances in the role of macrophages in nonalcoholic fatty liver disease[J]. Journal of Clinical Hepatology, 2020, 36(3): 680-683. doi: 10.3969/j.issn.1001-5256.2020.03.046
    [18]Zhou ZhenHua, Wang LingTai, Gao YueQiu. Role of hepatocyte mitophagy in the pathogenesis of nonalcoholic fatty liver disease[J]. Journal of Clinical Hepatology, 2019, 35(12): 2809-2811. doi: 10.3969/j.issn.1001-5256.2019.12.036
    [19]Liu SuTong, Zhao WenXia. Research advances in the pathogenesis of nonalcoholic fatty liver disease-related hepatocellular carcinoma[J]. Journal of Clinical Hepatology, 2019, 35(7): 1621-1625. doi: 10.3969/j.issn.1001-5256.2019.07.043
    [20]Gui WenFang, Zhu QingJing, Yang Ling. Research advances in nonalcoholic fatty liver disease-related hepatocellular carcinoma[J]. Journal of Clinical Hepatology, 2018, 34(12): 2693-2697. doi: 10.3969/j.issn.1001-5256.2018.12.040
  • 加载中
    Created with Highcharts 5.0.7Chart context menuAccess Class DistributionFULLTEXT: 15.5 %FULLTEXT: 15.5 %META: 78.2 %META: 78.2 %PDF: 6.3 %PDF: 6.3 %FULLTEXTMETAPDF
    Created with Highcharts 5.0.7Chart context menuAccess Area Distribution其他: 5.8 %其他: 5.8 %其他: 1.0 %其他: 1.0 %Bengaluru: 0.1 %Bengaluru: 0.1 %Central District: 0.1 %Central District: 0.1 %China: 0.4 %China: 0.4 %Germany: 0.1 %Germany: 0.1 %India: 0.3 %India: 0.3 %Kao-sung: 0.1 %Kao-sung: 0.1 %Osaka: 0.1 %Osaka: 0.1 %Reynoldsburg: 0.1 %Reynoldsburg: 0.1 %Russian Federation: 0.1 %Russian Federation: 0.1 %Saitama: 0.2 %Saitama: 0.2 %San Jose: 0.1 %San Jose: 0.1 %Seattle: 0.1 %Seattle: 0.1 %Secaucus: 0.1 %Secaucus: 0.1 %Taoyuan District: 0.1 %Taoyuan District: 0.1 %Ukraine: 0.1 %Ukraine: 0.1 %United States: 0.1 %United States: 0.1 %[]: 0.3 %[]: 0.3 %三明: 0.1 %三明: 0.1 %上海: 4.3 %上海: 4.3 %东莞: 1.1 %东莞: 1.1 %中山: 0.1 %中山: 0.1 %乌兰察布: 0.1 %乌兰察布: 0.1 %佛山: 0.2 %佛山: 0.2 %保定: 0.1 %保定: 0.1 %兰州: 0.2 %兰州: 0.2 %加利福尼亚州: 0.1 %加利福尼亚州: 0.1 %北京: 5.1 %北京: 5.1 %南京: 3.5 %南京: 3.5 %南宁: 0.4 %南宁: 0.4 %南昌: 0.5 %南昌: 0.5 %南通: 0.1 %南通: 0.1 %南阳: 0.1 %南阳: 0.1 %印度泰米尔纳德: 0.1 %印度泰米尔纳德: 0.1 %厦门: 0.2 %厦门: 0.2 %台州: 0.2 %台州: 0.2 %合肥: 0.5 %合肥: 0.5 %吉林: 0.1 %吉林: 0.1 %吉隆坡: 0.1 %吉隆坡: 0.1 %哈尔滨: 0.6 %哈尔滨: 0.6 %哥伦布: 0.1 %哥伦布: 0.1 %嘉兴: 0.1 %嘉兴: 0.1 %夏延: 0.2 %夏延: 0.2 %大理: 0.1 %大理: 0.1 %大连: 0.3 %大连: 0.3 %天津: 1.2 %天津: 1.2 %太原: 0.1 %太原: 0.1 %孟买: 0.1 %孟买: 0.1 %宁波: 0.2 %宁波: 0.2 %安康: 0.2 %安康: 0.2 %宜春: 0.2 %宜春: 0.2 %巴音郭楞: 0.1 %巴音郭楞: 0.1 %常德: 0.1 %常德: 0.1 %广州: 2.7 %广州: 2.7 %张家口: 1.3 %张家口: 1.3 %张家界: 0.1 %张家界: 0.1 %徐州: 0.1 %徐州: 0.1 %成都: 0.5 %成都: 0.5 %扬州: 0.4 %扬州: 0.4 %新乡: 0.1 %新乡: 0.1 %无锡: 0.6 %无锡: 0.6 %日照: 0.1 %日照: 0.1 %昆明: 0.7 %昆明: 0.7 %晋城: 0.1 %晋城: 0.1 %朝阳: 0.2 %朝阳: 0.2 %本溪: 0.1 %本溪: 0.1 %来宾: 0.1 %来宾: 0.1 %杭州: 2.6 %杭州: 2.6 %柳州: 0.1 %柳州: 0.1 %桂林: 0.2 %桂林: 0.2 %武汉: 1.1 %武汉: 1.1 %江门: 0.4 %江门: 0.4 %池州: 0.1 %池州: 0.1 %沈阳: 0.9 %沈阳: 0.9 %沧州: 0.1 %沧州: 0.1 %泉州: 0.1 %泉州: 0.1 %波士顿: 0.1 %波士顿: 0.1 %洛杉矶: 0.2 %洛杉矶: 0.2 %洛阳: 0.2 %洛阳: 0.2 %济南: 1.3 %济南: 1.3 %海口: 0.1 %海口: 0.1 %海得拉巴: 0.1 %海得拉巴: 0.1 %淄博: 0.1 %淄博: 0.1 %淮安: 0.1 %淮安: 0.1 %深圳: 0.6 %深圳: 0.6 %深圳市龙岗区: 0.1 %深圳市龙岗区: 0.1 %温州: 0.3 %温州: 0.3 %湘潭: 0.1 %湘潭: 0.1 %湘西: 0.1 %湘西: 0.1 %湛江: 0.4 %湛江: 0.4 %漯河: 0.2 %漯河: 0.2 %珠海: 0.2 %珠海: 0.2 %石家庄: 0.4 %石家庄: 0.4 %福州: 0.6 %福州: 0.6 %秦皇岛: 0.1 %秦皇岛: 0.1 %绥化: 0.1 %绥化: 0.1 %美国伊利诺斯芝加哥: 0.1 %美国伊利诺斯芝加哥: 0.1 %耶拿: 0.1 %耶拿: 0.1 %芒廷维尤: 31.8 %芒廷维尤: 31.8 %芝加哥: 0.2 %芝加哥: 0.2 %苏州: 0.6 %苏州: 0.6 %莫斯科: 1.0 %莫斯科: 1.0 %衡阳: 0.1 %衡阳: 0.1 %西宁: 7.9 %西宁: 7.9 %西安: 0.6 %西安: 0.6 %西雅图: 0.1 %西雅图: 0.1 %贵阳: 0.1 %贵阳: 0.1 %赣州: 0.4 %赣州: 0.4 %赤峰: 0.1 %赤峰: 0.1 %达拉斯: 0.1 %达拉斯: 0.1 %运城: 0.6 %运城: 0.6 %遵义: 0.1 %遵义: 0.1 %邯郸: 0.1 %邯郸: 0.1 %郑州: 0.2 %郑州: 0.2 %都伯林: 0.1 %都伯林: 0.1 %重庆: 2.3 %重庆: 2.3 %铁岭: 0.1 %铁岭: 0.1 %铜仁: 0.1 %铜仁: 0.1 %银川: 0.1 %银川: 0.1 %镇江: 0.1 %镇江: 0.1 %长春: 0.7 %长春: 0.7 %长沙: 4.6 %长沙: 4.6 %长治: 0.1 %长治: 0.1 %青岛: 1.4 %青岛: 1.4 %首尔: 0.1 %首尔: 0.1 %香港: 0.1 %香港: 0.1 %香港特别行政区: 0.1 %香港特别行政区: 0.1 %驻马店: 0.1 %驻马店: 0.1 %黄冈: 0.1 %黄冈: 0.1 %黄石: 0.1 %黄石: 0.1 %龙岩: 0.1 %龙岩: 0.1 %其他其他BengaluruCentral DistrictChinaGermanyIndiaKao-sungOsakaReynoldsburgRussian FederationSaitamaSan JoseSeattleSecaucusTaoyuan DistrictUkraineUnited States[]三明上海东莞中山乌兰察布佛山保定兰州加利福尼亚州北京南京南宁南昌南通南阳印度泰米尔纳德厦门台州合肥吉林吉隆坡哈尔滨哥伦布嘉兴夏延大理大连天津太原孟买宁波安康宜春巴音郭楞常德广州张家口张家界徐州成都扬州新乡无锡日照昆明晋城朝阳本溪来宾杭州柳州桂林武汉江门池州沈阳沧州泉州波士顿洛杉矶洛阳济南海口海得拉巴淄博淮安深圳深圳市龙岗区温州湘潭湘西湛江漯河珠海石家庄福州秦皇岛绥化美国伊利诺斯芝加哥耶拿芒廷维尤芝加哥苏州莫斯科衡阳西宁西安西雅图贵阳赣州赤峰达拉斯运城遵义邯郸郑州都伯林重庆铁岭铜仁银川镇江长春长沙长治青岛首尔香港香港特别行政区驻马店黄冈黄石龙岩

Catalog

    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

    Figures(2)  / Tables(5)

    Article Metrics

    Article views (1456) PDF downloads(118) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return