SCFAs alleviated steatosis and inflammation in mice with NASH induced by MCD

in Journal of Endocrinology
Authors:
Mingjuan Deng Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China

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Fang Qu Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Beijing Laboratory for Food Quality and Safety, China Agricultural University, Beijing, China

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Long Chen Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Research Center for Probiotics, China Agricultural University, Beijing, China

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Chang Liu Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Beijing Laboratory for Food Quality and Safety, China Agricultural University, Beijing, China

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Ming Zhang School of Food and Chemical Engineering, Beijing Technology and Business University, Beijing, China

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Fazheng Ren Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Beijing Laboratory for Food Quality and Safety, China Agricultural University, Beijing, China
Research Center for Probiotics, China Agricultural University, Beijing, China

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Huiyuan Guo Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Research Center for Probiotics, China Agricultural University, Beijing, China

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Hao Zhang Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Beijing Laboratory for Food Quality and Safety, China Agricultural University, Beijing, China

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Shaoyang Ge Research Center for Probiotics, China Agricultural University, Beijing, China
Hebei Engineering Research Center of Animal Product, Sanhe, China

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Chaodong Wu Department of Nutrition, Texas A&M University, College Station, Texas, USA

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Liang Zhao Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
Research Center for Probiotics, China Agricultural University, Beijing, China

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Correspondence should be addressed to C Wu or L Zhao: cdwu@tamu.edu or lzhao@cau.edu.cn
DOI:
https://doi.org/10.1530/JOE-20-0018
Volume/Issue:
Volume 245: Issue 3
Article Type:
Research Article
Page Range:
425–437
Online Publication Date:
Jun 2020
Copyright:
© 2020 Society for Endocrinology 2020
Restricted access
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This study aimed to assess the effects of three major SCFAs (acetate, propionate, and butyrate) on NASH phenotype in mice. C57BL/6 mice were fed a methionine- and choline-deficient (MCD) diet and treated with sodium acetate, sodium propionate, or sodium butyrate during the 6-week feeding period. SCFA treatment significantly reduced serum levels of alanine aminotransferase and aspartate transaminase, the numbers of lipid droplets, and the levels of triglycerides and cholesterols in livers of the mice compared with control treatment. SCFAs also reduced MCD-induced hepatic aggregation of macrophages and proinflammatory responses. Among the three SCFAs, sodium acetate (NaA) revealed the best efficacy at alleviating MCD-induced hepatic steatosis and inflammation. Additionally, NaA increased AMP-activated protein kinase activation in the liver and induced the expression of fatty acid oxidation gene in both the liver and cultured hepatocytes. In vitro, NaA decreased MCD-mimicking media-induced proinflammatory responses in macrophages to a greater extent than in hepatocytes. These results indicated that NaA alleviates steatosis in a manner involving AMPK activation. Also, NaA alleviation of hepatic inflammation appears to be due to, in large part, suppression of macrophage proinflammatory activation. SCFAs may represent as a novel and viable approach for alleviating NASH.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© 2020 Society for Endocrinology 2020
Page(s):
13
Article Type:
Research Article
Received Date:
12 Mar 2020
Accepted Date:
09 Apr 2020
Print Publication Date:
01 Jun 2020
Online Publication Date:
Jun 2020
Keywords:
short chain fatty acid; non-alcoholic steatohepatitis; steatosis; inflammation; macrophage

  • Bloemen JG, Venema K, van de Poll MC, Olde Damink SW, Buurman WA & Dejong CH 2009 Short chain fatty acids exchange across the gut and liver in humans measured at surgery. Clinical Nutrition 28 657–661. (https://doi.org/10.1016/j.clnu.2009.05.011)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Cai Y, Li H, Liu M, Pei Y, Zheng J, Zhou J, Luo X, Huang W, Ma L, Yang Q, et al. 2018 Disruption of adenosine 2A receptor exacerbates NAFLD through increasing inflammatory responses and SREBP1c activity. Hepatology 68 48–61. (https://doi.org/10.1002/hep.29777)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Canfora EE, Jocken JW & Blaak EE 2015 Short-chain fatty acids in control of body weight and insulin sensitivity. Nature Reviews: Endocrinology 11 577–591. (https://doi.org/10.1038/nrendo.2015.128)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, Harrison SA, Brunt EM & Sanyal AJ 2018 The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology 67 328–357. (https://doi.org/10.1002/hep.29367)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chambers ES, Byrne CS, Rugyendo A, Morrison DJ, Preston T, Tedford C, Bell JD, Thomas L, Akbar AN, Riddell NE, et al. 2019 The effects of dietary supplementation with inulin and inulin-propionate ester on hepatic steatosis in adults with non-alcoholic fatty liver disease. Diabetes, Obesity and Metabolism 21 372–376. (https://doi.org/10.1111/dom.13500)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chen J & Vitetta L 2018 Inflammation-modulating effect of butyrate in the prevention of colon cancer by dietary fiber. Clinical Colorectal Cancer 17 e541–e544. (https://doi.org/10.1016/j.clcc.2018.05.001)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Cool B, Zinker B, Chiou W, Kifle L, Cao N, Perham M, Dickinson R, Adler A, Gagne G, Iyengar R, et al. 2006 Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome. Cell Metabolism 3 403–416. (https://doi.org/10.1016/j.cmet.2006.05.005)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Dangana EO, Omolekulo TE, Areola ED, Olaniyi KS, Soladoye AO & Olatunji LA 2019 Sodium acetate protects against nicotine-induced excess hepatic lipid in male rats by suppressing xanthine oxidase activity. Chemico-Biological Interactions 316 108929.

    • PubMed
    • Search Google Scholar
    • Export Citation

  • den Besten G, Bleeker A, Gerding A, van Eunen K, Havinga R, van Dijk TH, Oosterveer MH, Jonker JW, Groen AK, Reijngoud DJ, et al. 2015 Short-chain fatty acids protect against high-fat diet-induced obesity via a PPARγ-dependent switch from lipogenesis to fat oxidation. Diabetes 64 2398–2408. (https://doi.org/10.2337/db14-1213)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Duarte SMB, Stefano JT & Oliveira CP 2019 Microbiota and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH). Annals of Hepatology 18 416–421. (https://doi.org/10.1016/j.aohep.2019.04.006)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Estes C, Razavi H, Loomba R, Younossi Z & Sanyal AJ 2018 Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology 67 123–133. (https://doi.org/10.1002/hep.29466)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Guo X, Li H, Xu H, Halim V, Thomas LN, Woo SL, Huo Y, Chen YE, Sturino JM & Wu C 2013 Disruption of inducible 6-phosphofructo-2-kinase impairs the suppressive effect of PPARgamma activation on diet-induced intestine inflammatory response. Journal of Nutritional Biochemistry 24 770–775. (https://doi.org/10.1016/j.jnutbio.2012.04.007)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hattori M, Kondo T, Kishi M & Yamagami K 2010 A single oral administration of acetic acid increased energy expenditure in C57BL/6J mice. Bioscience, Biotechnology, and Biochemistry 74 2158–2159. (https://doi.org/10.1271/bbb.100486)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hong YH, Nishimura Y, Hishikawa D, Tsuzuki H, Miyahara H, Gotoh C, Choi KC, Feng DD, Chen C, Lee HG, et al. 2005 Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43. Endocrinology 146 5092–5099. (https://doi.org/10.1210/en.2005-0545)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Huang W, Metlakunta A, Dedousis N, Zhang P, Sipula I, Dube JJ, Scott DK & O’Doherty RM 2010 Depletion of liver Kupffer cells prevents the development of diet-induced hepatic steatosis and insulin resistance. Diabetes 59 347–357. (https://doi.org/10.2337/db09-0016)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Jin CJ, Sellmann C, Engstler AJ, Ziegenhardt D & Bergheim I 2015 Supplementation of sodium butyrate protects mice from the development of non-alcoholic steatohepatitis (NASH). British Journal of Nutrition 114 1745–1755. (https://doi.org/10.1017/S0007114515003621)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kodama Y, Kisseleva T, Iwaisako K, Miura K, Taura K, De Minicis S, Osterreicher CH, Schnabl B, Seki E & Brenner DA 2009 C-Jun N-terminal kinase-1 from hematopoietic cells mediates progression from hepatic steatosis to steatohepatitis and fibrosis in mice. Gastroenterology 137 1467.e5–1477.e5. (https://doi.org/10.1053/j.gastro.2009.06.045)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Koh A, De Vadder F, Kovatcheva-Datchary P & Backhed F 2016 From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell 165 1332–1345. (https://doi.org/10.1016/j.cell.2016.05.041)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kohli R, Pan X, Malladi P, Wainwright MS & Whitington PF 2007 Mitochondrial reactive oxygen species signal hepatocyte steatosis by regulating the phosphatidylinositol 3-kinase cell survival pathway. Journal of Biological Chemistry 282 21327–21336. (https://doi.org/10.1074/jbc.M701759200)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Larter CZ, Yeh MM, Williams J, Bell-Anderson KS & Farrell GC 2008 MCD-induced steatohepatitis is associated with hepatic adiponectin resistance and adipogenic transformation of hepatocytes. Journal of Hepatology 49 407–416. (https://doi.org/10.1016/j.jhep.2008.03.026)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Li M, van Esch BCAM, Wagenaar GTM, Garssen J, Folkerts G & Henricks PAJ 2018a Pro- and anti-inflammatory effects of short chain fatty acids on immune and endothelial cells. European Journal of Pharmacology 831 52–59. (https://doi.org/10.1016/j.ejphar.2018.05.003)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Li Y, Zhang S, Wang Y, Peng J, Fang F & Yang X 2018b MLH1 enhances the sensitivity of human endometrial carcinoma cells to cisplatin by activating the MLH1/c-Abl apoptosis signaling pathway. BMC Cancer 18 1294. (https://doi.org/10.1186/s12885-018-5218-4)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lin HV, Frassetto A, Kowalik EJ Jr, Nawrocki AR, Lu MM, Kosinski JR, Hubert JA, Szeto D, Yao X, Forrest G, et al. 2012 Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS ONE 7 e35240. (https://doi.org/10.1371/journal.pone.0035240)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Liu T, Li J, Liu Y, Xiao N, Suo H, Xie K, Yang C & Wu C 2012 Short-chain fatty acids suppress lipopolysaccharide-induced production of nitric oxide and proinflammatory cytokines through inhibition of NF-kappaB pathway in RAW264.7 cells. Inflammation 35 1676–1684. (https://doi.org/10.1007/s10753-012-9484-z)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Luo X, Li H, Ma L, Zhou J, Guo X, Woo SL, Pei Y, Knight LR, Deveau M, Chen Y, et al. 2018 Expression of STING is increased in liver tissues from patients with NAFLD and promotes macrophage-mediated hepatic inflammation and fibrosis in mice. Gastroenterology 155 1971.e4–1984.e4. (https://doi.org/10.1053/j.gastro.2018.09.010)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Mridha AR, Wree A, Robertson AAB, Yeh MM, Johnson CD, Van Rooyen DM, Haczeyni F, Teoh NC, Savard C, Ioannou GN, et al. 2017 NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice. Journal of Hepatology 66 1037–1046. (https://doi.org/10.1016/j.jhep.2017.01.022)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Nugent C & Younossi ZM 2007 Evaluation and management of obesity-related nonalcoholic fatty liver disease. Nature Clinical Practice: Gastroenterology and Hepatology 4 432–441. (https://doi.org/10.1038/ncpgasthep0879)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Oliphant K & Allen-Vercoe E 2019 Macronutrient metabolism by the human gut microbiome: major fermentation by-products and their impact on host health. Microbiome 7 91. (https://doi.org/10.1186/s40168-019-0704-8)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Papathanasopoulos A & Camilleri M 2010 Dietary fiber supplements: effects in obesity and metabolic syndrome and relationship to gastrointestinal functions. Gastroenterology 138 65.e1–72.e1. (https://doi.org/10.1053/j.gastro.2009.11.045)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sahai A, Pan X, Paul R, Malladi P, Kohli R & Whitington PF 2006 Roles of phosphatidylinositol 3-kinase and osteopontin in steatosis and aminotransferase release by hepatocytes treated with methionine-choline-deficient medium. American Journal of Physiology: Gastrointestinal and Liver Physiology 291 G55–G62. (https://doi.org/10.1152/ajpgi.00360.2005)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sahuri-Arisoylu M, Brody LP, Parkinson JR, Parkes H, Navaratnam N, Miller AD, Thomas EL, Frost G & Bell JD 2016 Reprogramming of hepatic fat accumulation and ‘browning’ of adipose tissue by the short-chain fatty acid acetate. International Journal of Obesity 40 955–963. (https://doi.org/10.1038/ijo.2016.23)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, Manchester JK, Hammer RE, Williams SC, Crowley J, Yanagisawa M, et al. 2008 Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. PNAS 105 16767–16772. (https://doi.org/10.1073/pnas.0808567105)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sanyal AJ 2005 Mechanisms of disease: pathogenesis of nonalcoholic fatty liver disease. Nature Clinical Practice: Gastroenterology and Hepatology 2 46–53. (https://doi.org/10.1038/ncpgasthep0084)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Shi H, Bi H, Sun X, Dong H, Jiang Y, Mu H, Liu G, Kong W, Gao R & Su J 2018 Antitumor effects of Tubeimoside-1 in NCI-H1299 cells are mediated by microRNA-126-5p-induced inactivation of VEGF-A/VEGFR-2/ERK signaling pathway. Molecular Medicine Reports 17 4327–4336. (https://doi.org/10.3892/mmr.2018.8459)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Shin ES, Cho SY, Lee EH, Lee SJ, Chang IS & Lee TR 2006 Positive regulation of hepatic carnitine palmitoyl transferase 1A (CPT1A) activities by soy isoflavones and L-carnitine. European Journal of Nutrition 45 159–164.

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Srivastava AR, Kumar S, Agarwal GG & Ranjan P 2007 Blunt abdominal injury: serum ALT-A marker of liver injury and a guide to assessment of its severity. Injury 38 1069–1074. (https://doi.org/10.1016/j.injury.2007.04.019)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Tobita H, Sato S, Yazaki T, Mishiro T, Ishimura N, Ishihara S & Kinoshita Y 2018 Alogliptin alleviates hepatic steatosis in a mouse model of nonalcoholic fatty liver disease by promoting CPT1a expression via Thr172 phosphorylation of AMPKalpha in the liver. Molecular Medicine Reports 17 6840–6846.

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E, Cameron J, Grosse J, Reimann F & Gribble FM 2012 Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 61 364–371. (https://doi.org/10.2337/db11-1019)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • van der Beek CM, Canfora EE, Kip AM, Gorissen SHM, Olde Damink SWM, van Eijk HM, Holst JJ, Blaak EE, Dejong CHC & Lenaerts K 2018 The prebiotic inulin improves substrate metabolism and promotes short-chain fatty acid production in overweight to obese men. Metabolism: Clinical and Experimental 87 25–35. (https://doi.org/10.1016/j.metabol.2018.06.009)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wu JL, Zou JY, Hu ED, Chen DZ, Chen L, Lu FB, Xu LM, Zheng MH, Li H, Huang Y, et al. 2017 Sodium butyrate ameliorates S100/FCA-induced autoimmune hepatitis through regulation of intestinal tight junction and toll-like receptor 4 signaling pathway. Immunology Letters 190 169–176. (https://doi.org/10.1016/j.imlet.2017.08.005)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wu W, Wang S, Liu Q, Wang X, Shan T & Wang Y 2018 Cathelicidin-WA attenuates LPS-induced inflammation and redox imbalance through activation of AMPK signaling. Free Radical Biology and Medicine 129 338–353. (https://doi.org/10.1016/j.freeradbiomed.2018.09.045)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Yamashita H 2016 Biological function of acetic acid-improvement in obesity and glucose tolerance by acetic acid in type 2 diabetic rats. Critical Reviews in Food Science and Nutrition 56 (Supplement 1) S171–S175. (https://doi.org/10.1080/10408398.2015.1045966)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Yamashita H, Fujisawa K, Ito E, Idei S, Kawaguchi N, Kimoto M, Hiemori M & Tsuji H 2007 Improvement of obesity and glucose tolerance by acetate in Type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Bioscience, Biotechnology, and Biochemistry 71 1236–1243. (https://doi.org/10.1271/bbb.60668)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ye J, Lv L, Wu W, Li Y, Shi D, Fang D, Guo F, Jiang H, Yan R, Ye W, et al. 2018 Butyrate protects mice against methionine-choline-deficient diet-induced non-alcoholic steatohepatitis by improving gut barrier function, attenuating inflammation and reducing endotoxin levels. Frontiers in Microbiology 9 1967. (https://doi.org/10.3389/fmicb.2018.01967)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Younossi Z, Anstee QM, Marietti M, Hardy T, Henry L, Eslam M, George J & Bugianesi E 2018 Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nature Reviews: Gastroenterology and Hepatology 15 11–20. (https://doi.org/10.1038/nrgastro.2017.109)

    • PubMed
    • Search Google Scholar
    • Export Citation