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http://dx.doi.org/10.1038/s12276-018-0183-1

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)
Publication Information
Experimental and Molecular Medicine / v.50, no.12, 2018 , pp. 2.1-2.12 More about this Journal
Abstract
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.
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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).   DOI
2 Fan, J. G., Kim, S. U. & Wong, V. W. Newtrends on obesity and NAFLD in Asia. J. Hepatol. 67, 862-873 (2017).   DOI
3 Rinella, M. E. Nonalcoholic fatty liver disease. JAMA 313, 2263 (2015).   DOI
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).   DOI
5 Gao, Z. et al. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes 58, 1509-1517 (2009).   DOI
6 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).   DOI
7 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).   DOI
8 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).   DOI
9 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).   DOI
10 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).   DOI
11 Smits, M. M. et al. GLP-1 based therapies: clinical implications for gastroenterologists. Gut 65, 702-711 (2016).   DOI
12 Clarke, G. et al. Minireview: gut microbiota: the neglected endocrine organ. Mol. Endocrinol. 28, 1221-1238 (2014).   DOI
13 Tremaroli, V. & Backhed, F. Functional interactions between the gut microbiota and host metabolism. Nature 489, 242-249 (2012).   DOI
14 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).   DOI
15 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).   DOI
16 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).   DOI
17 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).   DOI
18 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).   DOI
19 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).   DOI
20 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).   DOI
21 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).   DOI
22 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).   DOI
23 Guilloteau, P. et al. From the gut to the peripheral tissues: the multiple effects of butyrate. Nutr. Res. Rev. 23, 366-384 (2010).   DOI
24 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).   DOI
25 Gkolfakis, P., Dimitriadis, G. & Triantafyllou, K. Gut microbiota and non-alcoholic fatty liver disease. Hepatobiliary Pancreat. Dis. Int. 14, 572-581 (2015).   DOI
26 Marchesi, J. R. et al. The gut microbiota and host health: a new clinical frontier. Gut 65, 330-339 (2016).   DOI
27 Steliou, K., Boosalis, M. S., Perrine, S. P., Sangerman, J. & Faller, D. V. Butyrate histone deacetylase inhibitors. Biores. Open Access 1, 192-198 (2012).   DOI
28 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).
29 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).   DOI
30 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).   DOI
31 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).   DOI
32 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).   DOI
33 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).   DOI
34 Zhou, D. et al. Prolyl oligopeptidase inhibition attenuates steatosis in the L02 human liver cell line. PLoS ONE 11, e0165224 (2016).   DOI
35 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).   DOI
36 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).   DOI
37 Gomez-Lechon, M. J. et al. A human hepatocellular in vitro model to investigate steatosis. Chem. Biol. Interact. 165, 106-116 (2007).   DOI
38 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).   DOI
39 Kleiner, D. E. et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41, 1313-1321 (2005).   DOI