APPLE POLYPHENOLS EXTRACT ALLEVIATES ABNORMALITES OF HEPATIC LIPID METABOLISM IN DSS-INDUCED ACUTE ULCERATIVE COLITIS MICE

LI Xin-ran, QIAN Qing-fan, MA Jie-yu, LUAN Wen-xue, LI Xin-li

Acta Nutrimenta Sinica ›› 2025, Vol. 47 ›› Issue (5) : 477-485.

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Acta Nutrimenta Sinica ›› 2025, Vol. 47 ›› Issue (5) : 477-485.
ORIGINAL ARTICLES

APPLE POLYPHENOLS EXTRACT ALLEVIATES ABNORMALITES OF HEPATIC LIPID METABOLISM IN DSS-INDUCED ACUTE ULCERATIVE COLITIS MICE

  • LI Xin-ran, QIAN Qing-fan, MA Jie-yu, LUAN Wen-xue, LI Xin-li
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Abstract

Objective To investigate the effects of apple polyphenol extract (APE) on the changes of hepatic lipid metabolism induced by dextran sodium sulfate (DSS) in mice with acute ulcerative colitis (UC) and the underlying mechanisms. Methods Thirty male C57BL/6 mice aged 6-8 weeks were randomly divided into three groups, namely control (CON), DSS model (DSS) and DSS model treated with APE (AD). All mice were fed the chow diet. Mice in CON group were given distilled water for 6 weeks. For mice in the DSS group, distilled water was provided for the first 5 weeks and 3% DSS (m/v) solution in drinking water was given for the last week. For mice in the AD group, distilled water was provided provided for the first 5 weeks and 3% DSS (m/v) solution in drinking water was given for the last week, simultaneously with 500 mg/(kg·bw) APE gavage for 6 weeks. After the intervention, blood samples from the angular vein were obtained, while colon and liver were collected for subsequent histological examination. Quantitative real time polymerase chain reaction (RT-qPCR) was employed to detect the mRNA expression of genes related to hepatic lipid metabolism. Results APE intervention significantly reduced DAI scores in UC mice, ameliorated colonic pathological damages, diminished hepatic lipid deposition and inflammatory cell infiltration, reduced NAS, and along with significantly reduced serum levels of TG, AST, ALT, as well as levels of TNF-α, IL-6 and IL-1β. Further mRNA analysis showed that compared with the CON group, the mRNA expression levels of the fatty acid oxidation-related genes Pparα, fatty acid uptake gene Cd36, lipolysis gene Atgl, cholesterol reverse transporter genes Abcg8, bile acid synthesis genes Cyp7a1 and the key regulator of hepatic lipid metabolism Sirt1 were significantly decreased (P<0.05). The mRNA levels of Acc, Tgr5, ‌proinflammatory cytokine Tnf-α and Il-6 were significantly increased (P<0.05). Compared with the DSS group, APE intervention significantly increased the mRNA expression levels of Sirt1, Sr-b1 and Lxrα (P<0.05),reduced the mRNA expression levels of Acc, Tgr5 and Tnf-α (P<0.05). Conclusion APE improves acute UC-associated hepatic lipid metabolism abnormalities by regulating the mRNA levels of hepatic lipid metabolism-related genes.

Key words

apple polyphenols extract / dextran sodium sulfate / acute ulcerative colitis / liver / lipid metabolism

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LI Xin-ran, QIAN Qing-fan, MA Jie-yu, LUAN Wen-xue, LI Xin-li. APPLE POLYPHENOLS EXTRACT ALLEVIATES ABNORMALITES OF HEPATIC LIPID METABOLISM IN DSS-INDUCED ACUTE ULCERATIVE COLITIS MICE[J]. Acta Nutrimenta Sinica. 2025, 47(5): 477-485

References

[1] Feuerstein JD, Moss AC, Farraye FA.Ulcerative colitis[J]. Mayo Clin Proc, 2019, 94: 1357–1373.
[2] Gajendran M, Loganathan P, Jimenez G, et al. A comprehensive review and update on ulcerative colitis[J]. Dis Mon, 2019, 65: 100851.
[3] Le Berre C, Honap S, Peyrin-Biroulet L.Ulcerative colitis[J]. Lancet, 2023, 402: 571–584.
[4] 阎鹏光, 李景南. 溃疡性结肠炎的规范诊治[J]. 中华内科杂志, 2021,60: 567–570.
[5] Gros B, Kaplan GG.Ulcerative colitis in adults: a review[J]. JAMA, 2023, 330: 951–965.
[6] Fan F, Mundra PA, Fang L, et al. Lipidomic profiling in inflammatory bowel disease: comparison between ulcerative colitis and crohn's disease[J]. Inflamm Bowel Dis, 2015, 21: 1511–1518.
[7] Hernández-Camba A, Carrillo-Palau M, Ramos L, et al. Apolipoprotein C3 is downregulated in patients with inflammatory bowel disease[J]. Clin Transl Gastroenterol, 2022, 13: e00500.
[8] Gupta A, Vuyyuru SK, Kante B, et al. Prevalence, predictors, and impact of hepatic steatosis in patients with ulcerative colitis: a prospective observational cohort study[J]. J Clin Exp Hepatol, 2024, 14: 101293.
[9] Restellini S, Chazouillères O, Frossard JL.Hepatic manifestations of inflammatory bowel diseases[J]. Liver Int, 2017, 37: 475–489.
[10] Katsandegwaza B, Horsnell W, Smith K.Inflammatory bowel disease: a review of pre-clinical murine models of human disease[J]. Int J Mol Sci, 2022, 23: 19.
[11] Limketkai BN, Hamideh M, Shah R, et al. Dietary patterns and their association with symptoms activity in inflammatory bowel diseases[J]. Inflamm Bowel Dis, 2022, 28: 1627–1636.
[12] Ananthakrishnan AN, Khalili H, Konijeti GG, et al. A prospective study of long-term intake of dietary fiber and risk of Crohn's disease and ulcerative colitis[J]. Gastroenterology, 2013, 145: 970–977.
[13] Levine A, Sigall Boneh R, Wine E.Evolving role of diet in the pathogenesis and treatment of inflammatory bowel diseases[J]. Gut, 2018, 67: 1726–1738.
[14] 李旋, 毕金峰, 刘璇, 等. 苹果多酚的组成和功能特性研究现状与展望[J].中国食品学报, 2020, 20: 328-340.
[15] 蔡朋举, 孙爱东, 贾国梁. 植物多酚的抗炎功效及微胶囊化研究进展[J].中国食品学报, 2022, 22: 417–427.
[16] Yan B, Chen L, Wang Y, et al. Preventive effect of apple polyphenol extract on high-fat diet-induced hepatic steatosis in mice through alleviating endoplasmic reticulum stress[J]. J Agric Food Chem, 2022, 70: 3172–3180.
[17] Li D, Liu F, Wang X, Li X.Apple polyphenol extract alleviates high-fat-diet-induced hepatic steatosis in male C57BL/6 mice by targeting LKB1/AMPK pathway[J]. J Agric Food Chem, 2019, 67: 12208–12218.
[18] Li D, Cui Y, Wang X, et al. Apple polyphenol extract alleviates lipid accumulation in free-fatty-acid-exposed HepG2 cells via activating autophagy mediated by SIRT1/AMPK signaling[J]. Phytother Res, 2021, 35: 1416–1431.
[19] Denis MC, Roy D, Yeganeh PR, et al. Apple peel polyphenols: a key player in the prevention and treatment of experimental inflammatory bowel disease[J]. Clin Sci, 2016, 130: 2217–2237.
[20] Liu F, Wang X, Li D, et al. Apple polyphenols extract alleviated dextran sulfate sodium-induced ulcerative colitis in C57BL/6 male mice by restoring bile acid metabolism disorder and gut microbiota dysbiosis[J]. Phytother Res, 2021, 35: 1468–1485.
[21] Rangan P, Choi I, Wei M, ,et al. Fasting-mimicking diet modulates microbiota. Fasting-mimicking diet modulates microbiota and promotes intestinal regeneration to reduce inflammatory bowel disease pathology[J]. Cell Rep, 2019, 26: 2704–19.e6.
[22] Marchal Bressenot A, Riddell RH, Boulagnon-Rombi C, et al. Review article: the histological assessment of disease activity in ulcerative colitis[J]. Aliment Pharmacol Ther, 2015, 42: 957–967.
[23] Gill RM, Kakar S.Nonalcoholic steatohepatitis: diagnostic challenges[J]. Surg Pathol Clin, 2013, 6: 227–257.
[24] Glassner K, Malaty HM, Abraham BP.Epidemiology and risk factors of nonalcoholic fatty liver disease among patients with inflammatory bowel disease[J]. Inflamm Bowel Dis, 2017, 23: 998–1003.
[25] Nagasako-Akazome Y, Kanda T, Ohtake Y, et al. Apple polyphenols influence cholesterol metabolism in healthy subjects with relatively high body mass index[J]. Oleo Sci, 2007, 56: 417–428.
[26] Akazome Y, Kametani N, Kanda T, et al. Evaluation of safety of excessive intake and efficacy of long-term intake of beverages containing apple polyphenols[J]. Oleo Sci, 2010, 5: 321–338.
[27] Ding RB, Bao J, Deng CX.Emerging roles of SIRT1 in fatty liver diseases[J]. Int J Biol Sci, 2017, 13: 852–867.
[28] Itoh N.FGF21 as a hepatokine, adipokine, and myokine in metabolism and diseases[J]. Front Endocrinol (Lausanne), 2014, 5: 107.
[29] He Y, Lu L, Wei X, et al. The multimerization and secretion of adiponectin are regulated by TNF-alpha[J]. Endocrine, 2016, 51: 456–468.
[30] Jin D, Sun J, Huang J, et al. TNF-α reduces g0s2 expression and stimulates lipolysis through PPAR-γ inhibition in 3T3-L1 adipocytes[J]. Cytokine, 2014, 69: 196–205.
[31] 曹瑞,季爱玲,张文斌,等.共轭亚油酸对肥胖大鼠肝脏脂质代谢酶及PPARγ基因表达的影响[J].军事医学科学院院刊,2007,31:42-45,49.
[32] Chiang JYL, Ferrell JM.Bile acid metabolism in liver pathobiology[J]. Gene Expression, 2018, 18: 71–87.
[33] Karaivazoglou K, Konstantakis C, Tourkochristou E, et al. Non-alcoholic fatty liver disease in inflammatory bowel disease patients[J]. Eur J Gastroenterol Hepatol, 2020, 32: 903–906.
[34] Purushotham A, Schug TT, Xu Q, et al. Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation[J]. Cell Metab, 2009, 9: 327–338.
[35] [35] de Gregorio E, Colell A, Morales A, et al. Relevance of SIRT1-NF-κB axis as therapeutic target to ameliorate inflammation in liver disease[J]. Int J Mol Sci, 2020, 21: 24.
[36] Lin QQ, Yan CF, Lin R, et al. SIRT1 regulates TNF-alpha-induced expression of CD40 in 3T3-L1 adipocytes via NF-kappaB pathway[J]. Cytokine, 2012, 60: 447–455.
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