Experimental and Molecular Medicine

  • 제50권12호
  • /
  • Pages.2.1-2.12
  • /
  • 2018
  • /
  • 1226-3613(pISSN)
  • /
  • 2092-6413(eISSN)
생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biongy)
권호 표지
DOI QR코드

DOI QR Code

Sodium butyrate reduces high-fat diet-induced non-alcoholic steatohepatitis through upregulation of hepatic GLP-1R expression

  • Zhou, Da (Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine) ;
  • Chen, Yuan-Wen (Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine) ;
  • Zhao, Ze-Hua (Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine) ;
  • Yang, Rui-Xu (Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine) ;
  • Xin, Feng-Zhi (Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine) ;
  • Liu, Xiao-Lin (Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine) ;
  • Pan, Qin (Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine) ;
  • Zhou, Huiping (Department of Microbiology and Immunology, Department of Internal Medicine/GI Division, McGuire VA Medical Center) ;
  • Fan, Jian-Gao (Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine)
  • 투고 : 2018.07.31
  • 심사 : 2018.09.06
  • 발행 : 2018.12.30
⟨ 이전 논문 다음 논문 ⟩

초록

Glucagon-like peptide-1 (GLP-1) has a broad spectrum of biological activity by regulating metabolic processes via both the direct activation of the class B family of G protein-coupled receptors and indirect nonreceptor-mediated pathways. GLP-1 receptor (GLP-1R) agonists have significant therapeutic effects on non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in animal models. However, clinical studies indicated that GLP-1 treatment had little effect on hepatic steatosis in some NAFLD patients, suggesting that GLP-1 resistance may occur in these patients. It is well-known that the gut metabolite sodium butyrate (NaB) could promote GLP-1 secretion from intestinal L cells. However, it is unclear whether NaB improves hepatic GLP-1 responsiveness in NAFLD. In the current study, we showed that the serum GLP-1 levels of NAFLD patients were similar to those of normal controls, but hepatic GLP-1R expression was significantly downregulated in NAFLD patients. Similarly, in the NAFLD mouse model, mice fed with a high-fat diet showed reduced hepatic GLP-1R expression, which was reversed by NaB treatment and accompanied by markedly alleviated liver steatosis. In addition, NaB treatment also upregulated the hepatic p-AMPK/p-ACC and insulin receptor/insulin receptor substrate-1 expression levels. Furthermore, NaB-enhanced GLP-1R expression in HepG2 cells by inhibiting histone deacetylase-2 independent of GPR43/GPR109a. These results indicate that NaB is able to prevent the progression of NAFL to NASH via promoting hepatic GLP-1R expression. NaB is a GLP-1 sensitizer and represents a potential therapeutic adjuvant to prevent NAFL progression to NASH.

키워드

과제정보

연구 과제 주관 기관 : National Natural Science Foundation of China

참고문헌

  1. Wang, F. S., Fan, J. G., Zhang, Z., Gao, B. & Wang, H. Y. The global burden of liver disease: the major impact of China. Hepatology 60, 2099-2108 (2014). https://doi.org/10.1002/hep.27406
  2. Fan, J. G., Kim, S. U. & Wong, V. W. Newtrends on obesity and NAFLD in Asia. J. Hepatol. 67, 862-873 (2017). https://doi.org/10.1016/j.jhep.2017.06.003
  3. Rinella, M. E. Nonalcoholic fatty liver disease. JAMA 313, 2263 (2015). https://doi.org/10.1001/jama.2015.5370
  4. Park, J. S., Lee, E. J., Lee, J. C., Kim, W. K. & Kim, H. S. Anti-inflammatory effects of short chain fatty acids in IFN-gamma-stimulated RAW 264.7 murine macrophage cells: involvement of NF-kappaB and ERK signaling pathways. Int. Immunopharmacol. 7, 70-77 (2007). https://doi.org/10.1016/j.intimp.2006.08.015
  5. Gao, Z. et al. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes 58, 1509-1517 (2009). https://doi.org/10.2337/db08-1637
  6. Zhang, W. H. et al. Sodium butyrate maintains growth performance by regulating the immune response in broiler chickens. Br. Poult. Sci. 52, 292-301 (2011). https://doi.org/10.1080/00071668.2011.578121
  7. Wen, Z.-S., Lu, J.-J. & Zou, X.-T. Effects of sodium butyrate on the intestinal morphology and DNA-binding activity of intestinal nuclear factor-:EB in weanling pigs. J. Anim. Vet. Adv. 11, 814-821 (2012). https://doi.org/10.3923/javaa.2012.814.821
  8. Yadav, H., Lee, J. H., Lloyd, J., Walter, P. & Rane, S. G. Beneficial metabolic effects of a probiotic via butyrate-induced GLP-1 hormone secretion. J. Biol. Chem. 288, 25088-25097 (2013). https://doi.org/10.1074/jbc.M113.452516
  9. Chambers, E. S., Morrison, D. J. & Frost, G. Control of appetite and energy intake by SCFA: what are the potential underlying mechanisms? Proc. Nutr. Soc. 74, 328-336 (2015). https://doi.org/10.1017/S0029665114001657
  10. Zhou, D. et al. Sodium butyrate attenuates high-fat diet-induced steatohepatitis in mice by improving gut microbiota and gastrointestinal barrier. World J. Gastroenterol. 23, 60-75 (2017). https://doi.org/10.3748/wjg.v23.i1.60
  11. Zhou, D. et al. Clostridium butyricum B1 alleviates high-fat diet-induced steatohepatitis in mice via enterohepatic immunoregulation. J. Gastroenterol. Hepatol. 32, 1640-1648 (2017). https://doi.org/10.1111/jgh.13742
  12. Kaji, I., Karaki, S.-i & Kuwahara, A. Short-chain fatty acid receptor and its contribution to glucagon-like peptide-1 release. Digestion 89, 31-36 (2014). https://doi.org/10.1159/000356211
  13. Cd, Graaf et al. Glucagon-like peptide-1 and its class B G protein-coupled receptors: a long march to therapeutic successes. Pharmacol. Rev. 68, 954-1013 (2016). https://doi.org/10.1124/pr.115.011395
  14. Ben-Shlomo, S. et al. Glucagon-like peptide-1 reduces hepatic lipogenesis via activation of AMP-activated protein kinase. J. Hepatol. 54, 1214-1223 (2011). https://doi.org/10.1016/j.jhep.2010.09.032
  15. Svegliati-Baroni, G. et al. Glucagon-like peptide-1 receptor activation stimulates hepatic lipid oxidation and restores hepatic signalling alteration induced by a high-fat diet in nonalcoholic steatohepatitis. Liver Int. 31, 1285-1297 (2011). https://doi.org/10.1111/j.1478-3231.2011.02462.x
  16. Trevaskis, J. L. et al. Glucagon-like peptide-1 receptor agonism improves metabolic, biochemical, and histopathological indices of nonalcoholic steatohepatitis in mice. Am. J. Physiol. Gastrointest. Liver Physiol. 302, G762-G772 (2012). https://doi.org/10.1152/ajpgi.00476.2011
  17. Ao, N., Yang, J., Wang, X. & Du, J. Glucagon-like peptide-1 preserves nonalcoholic fatty liver disease through inhibition of the endoplasmic reticulum stress-associated pathway. Hepatol. Res. 46, 343-353 (2016). https://doi.org/10.1111/hepr.12551
  18. Tang, A. et al. Effects of insulin glargine and liraglutide therapy on liver fat as measured by magnetic resonance in patients with type 2 diabetes: a randomized trial. Diabetes Care 38, 1339-1346 (2015). https://doi.org/10.2337/dc14-2548
  19. Smits, M. M. et al. Twelve week liraglutide or sitagliptin does not affect hepatic fat in type 2 diabetes: a randomised placebo-controlled trial. Diabetologia 59, 2588-2593 (2016). https://doi.org/10.1007/s00125-016-4100-7
  20. Grasset, E. et al. A specific gut microbiota dysbiosis of type 2 diabetic mice induces GLP-1 resistance through an enteric NO-dependent and gut-brain axis mechanism. Cell. Metab. 25, 1075-1090 e5 (2017). https://doi.org/10.1016/j.cmet.2017.04.013
  21. Bedossa, P. Utility and appropriateness of the fatty liver inhibition of progression (FLIP) algorithm and steatosis, activity, and fibrosis (SAF) score in the evaluation of biopsies of nonalcoholic fatty liver disease. Hepatology 60, 565-575 (2014). https://doi.org/10.1002/hep.27173
  22. Gomez-Lechon, M. J. et al. A human hepatocellular in vitro model to investigate steatosis. Chem. Biol. Interact. 165, 106-116 (2007). https://doi.org/10.1016/j.cbi.2006.11.004
  23. Zhou, D. et al. Prolyl oligopeptidase inhibition attenuates steatosis in the L02 human liver cell line. PLoS ONE 11, e0165224 (2016). https://doi.org/10.1371/journal.pone.0165224
  24. Kleiner, D. E. et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41, 1313-1321 (2005). https://doi.org/10.1002/hep.20701
  25. Zhou, D. et al. Total fecal microbiota transplantation alleviates high-fat dietinduced steatohepatitis in mice via beneficial regulation of gut microbiota. Sci. Rep. 7, 1529 (2017). https://doi.org/10.1038/s41598-017-01751-y
  26. Dhir, G. & Cusi, K. Glucagon like peptide-1 receptor agonists for the management of obesity and non-alcoholic fatty liver disease: a novel therapeutic option. J. Invest. Med. 66, 7-10 (2018). https://doi.org/10.1136/jim-2017-000554
  27. Tolhurst, G. et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 61, 364-371 (2012). https://doi.org/10.2337/db11-1019
  28. Ohira, H., Tsutsui, W. & Fujioka, Y. Are short chain fatty acids in gut microbiota defensive players for inflammation and atherosclerosis? J. Atheroscler. Thromb. 24, 660-672 (2017). https://doi.org/10.5551/jat.RV17006
  29. Ding, X., Saxena, N. K., Lin, S., Gupta, N. A. & Anania, F. A. Exendin-4, a glucagonlike protein-1 (GLP-1) receptor agonist, reverses hepatic steatosis in ob/ob mice. Hepatology 43, 173-181 (2006). https://doi.org/10.1002/hep.21006
  30. Gupta, N. A. et al. Glucagon-like peptide-1 receptor is present on human hepatocytes and has a direct role in decreasing hepatic steatosis in vitro by modulating elements of the insulin signaling pathway. Hepatology 51, 1584-1592 (2010). https://doi.org/10.1002/hep.23569
  31. Smits, M. M. et al. GLP-1 based therapies: clinical implications for gastroenterologists. Gut 65, 702-711 (2016). https://doi.org/10.1136/gutjnl-2015-310572
  32. Clarke, G. et al. Minireview: gut microbiota: the neglected endocrine organ. Mol. Endocrinol. 28, 1221-1238 (2014). https://doi.org/10.1210/me.2014-1108
  33. Tremaroli, V. & Backhed, F. Functional interactions between the gut microbiota and host metabolism. Nature 489, 242-249 (2012). https://doi.org/10.1038/nature11552
  34. den Besten, G. et al. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J. Lipid Res. 54, 2325-2340 (2013). https://doi.org/10.1194/jlr.R036012
  35. Gkolfakis, P., Dimitriadis, G. & Triantafyllou, K. Gut microbiota and non-alcoholic fatty liver disease. Hepatobiliary Pancreat. Dis. Int. 14, 572-581 (2015). https://doi.org/10.1016/S1499-3872(15)60026-1
  36. Marchesi, J. R. et al. The gut microbiota and host health: a new clinical frontier. Gut 65, 330-339 (2016). https://doi.org/10.1136/gutjnl-2015-309990
  37. Guilloteau, P. et al. From the gut to the peripheral tissues: the multiple effects of butyrate. Nutr. Res. Rev. 23, 366-384 (2010). https://doi.org/10.1017/S0954422410000247
  38. Steliou, K., Boosalis, M. S., Perrine, S. P., Sangerman, J. & Faller, D. V. Butyrate histone deacetylase inhibitors. Biores. Open Access 1, 192-198 (2012). https://doi.org/10.1089/biores.2012.0223
  39. Cleophas, M. C. et al. Suppression of monosodium urate crystal-induced cytokine production by butyrate is mediated by the inhibition of class I histone deacetylases. Ann. Rheum. Dis. 75, 593-600 (2016).

피인용 문헌

  1. Role of gut microbial metabolites in nonalcoholic fatty liver disease vol.20, pp.4, 2019, https://doi.org/10.1111/1751-2980.12709
  2. Microbial metabolites in non-alcoholic fatty liver disease vol.25, pp.17, 2018, https://doi.org/10.3748/wjg.v25.i17.2019
  3. Trimethylamine N-oxide attenuates high-fat high-cholesterol diet-induced steatohepatitis by reducing hepatic cholesterol overload in rats vol.25, pp.20, 2018, https://doi.org/10.3748/wjg.v25.i20.2450
  4. Lipid-regulating properties of butyric acid and 4-phenylbutyric acid: Molecular mechanisms and therapeutic applications vol.144, pp.None, 2019, https://doi.org/10.1016/j.phrs.2019.04.002
  5. Gut Microbiota-Derived Components and Metabolites in the Progression of Non-Alcoholic Fatty Liver Disease (NAFLD) vol.11, pp.8, 2018, https://doi.org/10.3390/nu11081712
  6. Understanding Dietary Intervention-Mediated Epigenetic Modifications in Metabolic Diseases vol.11, pp.None, 2020, https://doi.org/10.3389/fgene.2020.590369
  7. Butyrate: A Review on Beneficial Pharmacological and Therapeutic Effect vol.16, pp.None, 2018, https://doi.org/10.2174/1573401316999201029210912
  8. Advances in the Involvement of Gut Microbiota in Pathophysiology of NAFLD vol.7, pp.None, 2020, https://doi.org/10.3389/fmed.2020.00361
  9. Connecting the Dots Between Inflammatory Bowel Disease and Metabolic Syndrome: A Focus on Gut-Derived Metabolites vol.12, pp.5, 2018, https://doi.org/10.3390/nu12051434
  10. Bifidobacterium adolescentis and Lactobacillus rhamnosus alleviate non-alcoholic fatty liver disease induced by a high-fat, high-cholesterol diet through modulation of different gut microbiota-depende vol.11, pp.7, 2018, https://doi.org/10.1039/c9fo02905b
  11. Gut Microbiota Metabolites in NAFLD Pathogenesis and Therapeutic Implications vol.21, pp.15, 2018, https://doi.org/10.3390/ijms21155214
  12. The Gut Microbiota at the Service of Immunometabolism vol.32, pp.4, 2018, https://doi.org/10.1016/j.cmet.2020.09.004
  13. Fmoc-amino acid-based hydrogel vehicle for delivery of amygdalin to perform neuroprotection vol.2, pp.None, 2018, https://doi.org/10.1016/j.smaim.2020.10.004
  14. Modulation of Short-Chain Fatty Acids as Potential Therapy Method for Type 2 Diabetes Mellitus vol.2021, pp.None, 2018, https://doi.org/10.1155/2021/6632266
  15. Clinicopathological and prognostic significance of ubiquitin‐specific peptidase 15 and its relationship with transforming growth factor‐β receptors in patients with pancreatic ductal vol.36, pp.2, 2018, https://doi.org/10.1111/jgh.15244
  16. Gut Microbiota, Glucose, Lipid, and Water-Electrolyte Metabolism in Children With Nonalcoholic Fatty Liver Disease vol.11, pp.None, 2021, https://doi.org/10.3389/fcimb.2021.683743
  17. New Drugs on the Block-Emerging Treatments for Nonalcoholic Steatohepatitis vol.9, pp.1, 2018, https://doi.org/10.14218/jcth.2020.00057
  18. A double‐edged sword: Role of butyrate in the oral cavity and the gut vol.36, pp.2, 2021, https://doi.org/10.1111/omi.12322
  19. Gut-Liver Axis in Nonalcoholic Fatty Liver Disease: the Impact of the Metagenome, End Products, and the Epithelial and Vascular Barriers vol.41, pp.2, 2021, https://doi.org/10.1055/s-0041-1723752
  20. A pro-inflammatory mediator USP11 enhances the stability of p53 and inhibits KLF2 in intracerebral hemorrhage vol.21, pp.None, 2018, https://doi.org/10.1016/j.omtm.2021.01.015
  21. Sodium butyrate ameliorates non‐alcoholic fatty liver disease by upregulating miR‐150 to suppress CXCR4 expression vol.48, pp.8, 2018, https://doi.org/10.1111/1440-1681.13497
  22. The interplay between host cellular and gut microbial metabolism in NAFLD development and prevention vol.131, pp.2, 2018, https://doi.org/10.1111/jam.14992
  23. Molecular and Pathophysiological Links between Metabolic Disorders and Inflammatory Bowel Diseases vol.22, pp.17, 2021, https://doi.org/10.3390/ijms22179139
  24. Novel approaches to intervene gut microbiota in the treatment of chronic liver diseases vol.35, pp.10, 2018, https://doi.org/10.1096/fj.202100939r
  25. Gut Microbiota-Related Cellular and Molecular Mechanisms in the Progression of Nonalcoholic Fatty Liver Disease vol.10, pp.10, 2018, https://doi.org/10.3390/cells10102634
  26. AST-120 Treatment Alters the Gut Microbiota Composition and Suppresses Hepatic Triglyceride Levels in Obese Mice vol.46, pp.4, 2018, https://doi.org/10.1080/07435800.2021.1927074
  27. The Effects of Butyrate on Induced Metabolic-Associated Fatty Liver Disease in Precision-Cut Liver Slices vol.13, pp.12, 2018, https://doi.org/10.3390/nu13124203
  28. Inflammatory and fibrotic mechanisms in NAFLD—Implications for new treatment strategies vol.291, pp.1, 2022, https://doi.org/10.1111/joim.13380