請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/83476完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 潘敏雄 | zh_TW |
| dc.contributor.advisor | MIN-XIONG PAN | en |
| dc.contributor.author | 劉健平 | zh_TW |
| dc.contributor.author | Chien-Ping Liu | en |
| dc.date.accessioned | 2023-03-19T21:08:29Z | - |
| dc.date.available | 2023-12-27 | - |
| dc.date.copyright | 2022-10-06 | - |
| dc.date.issued | 2022 | - |
| dc.date.submitted | 2002-01-01 | - |
| dc.identifier.citation | Andy, S. Y., & Keeffe, E. B. (2003). Elevated AST or ALT to nonalcoholic fatty liver disease: accurate predictor of disease prevalence? The American Journal of Gastroenterology, 98, 955.
Arab, J. P., Arrese, M., & Trauner, M. (2018). Recent insights into the pathogenesis of nonalcoholic fatty liver disease. Annual Review of Pathology: Mechanisms of Disease, 13, 321-350. Avramoglu, R. K., Basciano, H., & Adeli, K. (2006). Lipid and lipoprotein dysregulation in insulin resistant states. Clinica Chimica Acta, 368, 1-19. Bayerdörffer, E., Mannes, G., Ochsenkühn, T., Dirschedl, P., Wiebecke, B., & Paumgartner, G. (1995). Unconjugated secondary bile acids in the serum of patients with colorectal adenomas. Gut, 36, 268-273. Bjursell, M., Wedin, M., Admyre, T., Hermansson, M., Böttcher, G., Göransson, M., Lindén, D., Bamberg, K., Oscarsson, J., & Bohlooly-Y, M. (2013). Ageing Fxr deficient mice develop increased energy expenditure, improved glucose control and liver damage resembling NASH. PloS One, 8, e64721. Blüher, M. (2019). Obesity: global epidemiology and pathogenesis. Nature Reviews Endocrinology, 15, 288-298. Blüher, M. (2020). Metabolically healthy obesity. Endocrine Reviews, 41, bnaa004. Boursier, J., Mueller, O., Barret, M., Machado, M., Fizanne, L., Araujo‐Perez, F., Guy, C. D., Seed, P. C., Rawls, J. F., & David, L. A. (2016). The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota. Hepatology, 63, 764-775. Bradford, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry, 72, 248-254. Bugianesi, E., Moscatiello, S., Ciaravella, M., & Marchesini, G. (2010). Insulin resistance in nonalcoholic fatty liver disease. Current Pharmaceutical Design, 16, 1941-1951. Buzzetti, E., Pinzani, M., & Tsochatzis, E. A. (2016). The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism, 65, 1038-1048. Cao, H., Xu, M., Dong, W., Deng, B., Wang, S., Zhang, Y., Wang, S., Luo, S., Wang, W., & Qi, Y. (2017). Secondary bile acid‐induced dysbiosis promotes intestinal carcinogenesis. International Journal of Cancer, 140, 2545-2556. Carino, A., Cipriani, S., Marchianò, S., Biagioli, M., Santorelli, C., Donini, A., Zampella, A., Monti, M. C., & Fiorucci, S. (2017). BAR502, a dual FXR and GPBAR1 agonist, promotes browning of white adipose tissue and reverses liver steatosis and fibrosis. Scientific Reports, 7, 1-13. Chan, W. K., Tan, A. T. B., Vethakkan, S. R., Tah, P. C., Vijayananthan, A., & Goh, K. L. (2013). Non‐alcoholic fatty liver disease in diabetics–prevalence and predictive factors in a multiracial hospital clinic population in Malaysia. Journal of Gastroenterology and Hepatology, 28, 1375-1383. Changbumrung, S., Tungtrongchitr, R., Migasena, P., & Chamroenngan, S. (1990). Serum unconjugated primary and secondary bile acids in patients with cholangiocarcinoma and hepatocellular carcinoma. Journal of the Medical Association of Thailand, 73, 81-90. Chiang, J. Y. (2013). Bile acid metabolism and signaling. Comprehensive Physiology, 3, 1191. Chiang, J. Y., & Ferrell, J. M. (2019). Bile acids as metabolic regulators and nutrient sensors. Annual Review of Nutrition, 39, 175. Chiang, J. Y., & Ferrell, J. M. (2020). Bile acid receptors FXR and TGR5 signaling in fatty liver diseases and therapy. American Journal of Physiology-Gastrointestinal and Liver Physiology, 318, G554-G573. Chiang, J. Y., & Ferrell, J. M. (2020). Up to date on cholesterol 7 alpha-hydroxylase (CYP7A1) in bile acid synthesis. Liver Research, 4, 47-63. Choi, Y., Kim, Y., Ham, H., Park, Y., Jeong, H. S., & Lee, J. (2011). Nobiletin suppresses adipogenesis by regulating the expression of adipogenic transcription factors and the activation of AMP-activated protein kinase (AMPK). Journal of Agricultural and Food Chemistry, 59, 12843-12849. Chooi, Y. C., Ding, C., & Magkos, F. (2019). The epidemiology of obesity. Metabolism, 92, 6-10. Chow, M. D., Lee, Y. H., & Guo, G. L. (2017). The role of bile acids in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Molecular Aspects of Medicine, 56, 34-44. Cusi, K. (2009). Role of insulin resistance and lipotoxicity in non-alcoholic steatohepatitis. Clinics in Liver Disease, 13, 545-563. David, L. A., Maurice, C. F., Carmody, R. N., Gootenberg, D. B., Button, J. E., Wolfe, B. E., Ling, A. V., Devlin, A. S., Varma, Y., & Fischbach, M. A. (2014). Diet rapidly and reproducibly alters the human gut microbiome. Nature, 505, 559-563. Dawson, P. A., Hubbert, M., Haywood, J., Craddock, A. L., Zerangue, N., Christian, W. V., & Ballatori, N. (2005). The heteromeric organic solute transporter α-β, Ostα-Ostβ, is an ileal basolateral bile acid transporter. Journal of Biological Chemistry, 280, 6960-6968. Day, C. P., & James, O. F. (1998). Steatohepatitis: a tale of two “hits”? Gastroenterology, 114, 842-845. Del Chierico, F., Nobili, V., Vernocchi, P., Russo, A., De Stefanis, C., Gnani, D., Furlanello, C., Zandonà, A., Paci, P., & Capuani, G. (2017). Gut microbiota profiling of pediatric nonalcoholic fatty liver disease and obese patients unveiled by an integrated meta‐omics‐based approach. Hepatology, 65, 451-464. Devkota, S., Wang, Y., Musch, M. W., Leone, V., Fehlner-Peach, H., Nadimpalli, A., Antonopoulos, D. A., Jabri, B., & Chang, E. B. (2012). Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10−/− mice. Nature, 487, 104-108. Duan, Y., Zhang, F., Yuan, W., Wei, Y., Wei, M., Zhou, Y., Yang, Y., Chang, Y., & Wu, X. (2019). Hepatic cholesterol accumulation ascribed to the activation of ileum Fxr-Fgf15 pathway inhibiting hepatic Cyp7a1 in high-fat diet-induced obesity rats. Life Sciences, 232, 116638. Festi, D., Montagnani, M., Azzaroli, F., Lodato, F., Mazzella, G., Roda, A., Rita Di Biase, A., Roda, E., Simoni, P., & Colecchia, A. (2007). Clinical efficacy and effectiveness of ursodeoxycholic acid in cholestatic liver diseases. Current Clinical Pharmacology, 2, 155-177. Fu, T., Kim, Y. C., Byun, S., Kim, D. H., Seok, S., Suino-Powell, K., Xu, H. E., Kemper, B., & Kemper, J. K. (2016). FXR primes the liver for intestinal FGF15 signaling by transient induction of β-klotho. Molecular Endocrinology, 30, 92-103. Gadde, K. M., Martin, C. K., Berthoud, H. R., & Heymsfield, S. B. (2018). Obesity: pathophysiology and management. Journal of the American College of Cardiology, 71, 69-84. Gandhi, G. R., Vasconcelos, A. B. S., Wu, D. T., Li, H. B., Antony, P. J., Li, H., Geng, F., Gurgel, R. Q., Narain, N., & Gan, R.-Y. (2020). Citrus flavonoids as promising phytochemicals targeting diabetes and related complications: A systematic review of in vitro and in vivo studies. Nutrients, 12, 2907. Gao, Z., Gao, W., Zeng, S. L., Li, P., & Liu, E. H. (2018). Chemical structures, bioactivities and molecular mechanisms of citrus polymethoxyflavones. Journal of Functional Foods, 40, 498-509. Gerritsen, J., Hornung, B., Renckens, B., van Hijum, S. A., Dos Santos, V. A. M., Rijkers, G. T., Schaap, P. J., de Vos, W. M., & Smidt, H. (2017). Genomic and functional analysis of Romboutsia ilealis CRIBT reveals adaptation to the small intestine. PeerJ, 5, e3698. Gil-Campos, M., Cañete, R., & Gil, A. (2004). Adiponectin, the missing link in insulin resistance and obesity. Clinical Nutrition, 23, 963-974. Guilherme, A., Virbasius, J. V., Puri, V., & Czech, M. P. (2008). Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nature Reviews Molecular Cell Biology, 9, 367-377. Hagenbuch, B., & Meier, P. J. (1994). Molecular cloning, chromosomal localization, and functional characterization of a human liver Na+/bile acid cotransporter. The Journal of Clinical Investigation, 93, 1326-1331. Halilbasic, E., Fiorotto, R., Fickert, P., Marschall, H. U., Moustafa, T., Spirli, C., Fuchsbichler, A., Gumhold, J., Silbert, D., & Zatloukal, K. (2009). Side chain structure determines unique physiologic and therapeutic properties of norursodeoxycholic acid in Mdr2−/− mice. Hepatology, 49, 1972-1981. Harris, R., Card, T. R., Delahooke, T., Aithal, G. P., & Guha, I. N. (2019). Obesity is the most common risk factor for chronic liver disease: results from a risk stratification pathway using transient elastography. The American Journal of Gastroenterology, 114, 1744-1752. He, B., Jiang, J., Shi, Z., Wu, L., Yan, J., Chen, Z., Luo, M., Cui, D., Xu, S., & Yan, M. (2021). Pure total flavonoids from citrus attenuate non-alcoholic steatohepatitis via regulating the gut microbiota and bile acid metabolism in mice. Biomedicine and Pharmacotherapy, 135, 111183. Henao-Mejia, J., Elinav, E., Jin, C., Hao, L., Mehal, W. Z., Strowig, T., Thaiss, C. A., Kau, A. L., Eisenbarth, S. C., & Jurczak, M. J. (2012). Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature, 482, 179-185. Hruby, A., & Hu, F. B. (2015). The epidemiology of obesity: a big picture. Pharmacoeconomics, 33, 673-689. Inagaki, T., Choi, M., Moschetta, A., Peng, L., Cummins, C. L., McDonald, J. G., Luo, G., Jones, S. A., Goodwin, B., & Richardson, J. A. (2005). Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metabolism, 2, 217-225. Jahn, D., Kircher, S., Hermanns, H. M., & Geier, A. (2019). Animal models of NAFLD from a hepatologist's point of view. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1865, 943-953. Jiang, C., Xie, C., Li, F., Zhang, L., Nichols, R. G., Krausz, K. W., Cai, J., Qi, Y., Fang, Z.-Z., & Takahashi, S. (2015). Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease. The Journal of Clinical Investigation, 125, 386-402. Jones, B. V., Begley, M., Hill, C., Gahan, C. G., & Marchesi, J. R. (2008). Functional and comparative metagenomic analysis of bile salt hydrolase activity in the human gut microbiome. Proceedings of the National Academy of Sciences, 105, 13580-13585. Joyce, S. A., & Gahan, C. G. (2014). The gut microbiota and the metabolic health of the host. Current Opinion in Gastroenterology, 30, 120-127. Kim, Y. J., Choi, M. S., Woo, J. T., Jeong, M. J., Kim, S. R., & Jung, U. J. (2017). Long‐term dietary supplementation with low‐dose nobiletin ameliorates hepatic steatosis, insulin resistance, and inflammation without altering fat mass in diet‐induced obesity. Molecular Nutrition & Food Research, 61, 1600889. Kitahara, M., Takamine, F., Imamura, T., & Benno, Y. (2001). Clostridium hiranonis sp. nov., a human intestinal bacterium with bile acid 7alpha-dehydroxylating activity. International Journal of Systematic and Evolutionary Microbiology, 51, 39-44. Kong, B., Wang, L., Chiang, J. Y., Zhang, Y., Klaassen, C. D., & Guo, G. L. (2012). Mechanism of tissue‐specific farnesoid X receptor in suppressing the expression of genes in bile‐acid synthesis in mice. Hepatology, 56, 1034-1043. Konopelniuk, V. V., Goloborodko, I. I., Ishchuk, T. V., Synelnyk, T. B., Ostapchenko, L. I., Spivak, M. Y., & Bubnov, R. V. (2017). Efficacy of Fenugreek-based bionanocomposite on renal dysfunction and endogenous intoxication in high-calorie diet-induced obesity rat model—comparative study. EPMA Journal, 8, 377-390. Konstantinidi, M., & Koutelidakis, A. E. (2019). Functional foods and bioactive compounds: A review of its possible role on weight management and obesity’s metabolic consequences. Medicines, 6, 94. Kou, G., Li, P., Hu, Y., Chen, H., Nyantakyiwaa Amoah, A., Seydou Traore, S., Cui, Z., & Lyu, Q. (2021). Nobiletin activates thermogenesis of brown and white adipose tissue in high‐fat diet‐fed C57BL/6 mice by shaping the gut microbiota. The FASEB Journal, 35, e21267. Krishna‐Subramanian, S., Hanski, M., Loddenkemper, C., Choudhary, B., Pagès, G., Zeitz, M., & Hanski, C. (2012). UDCA slows down intestinal cell proliferation by inducing high and sustained ERK phosphorylation. International Journal of Cancer, 130, 2771-2782. Kumar, V., & Veeranjaneyulu, A. (2018). Herbs for Diabetes and Neurological Disease Management: Research and Advancements: CRC Press. Lai, C. S., Li, S., Chai, C. Y., Lo, C. Y., Dushenkov, S., Ho, C. T., Pan, M. H., & Wang, Y. J. (2008). Anti-inflammatory and antitumor promotional effects of a novel urinary metabolite, 3', 4'-didemethylnobiletin, derived from nobiletin. Carcinogenesis, 29, 2415-2424. Lau, L. H., & Wong, S. H. (2018). Microbiota, obesity and NAFLD. Obesity, Fatty Liver and Liver Cancer, 111-125. Le Roy, T., Llopis, M., Lepage, P., Bruneau, A., Rabot, S., Bevilacqua, C., Martin, P., Philippe, C., Walker, F., & Bado, A. (2013). Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice. Gut, 62, 1787-1794. Lee, Y. S., Cha, B. Y., Choi, S. S., Choi, B. K., Yonezawa, T., Teruya, T., Nagai, K., & Woo, J. T. (2013). Nobiletin improves obesity and insulin resistance in high-fat diet-induced obese mice. The Journal of Nutritional Biochemistry, 24, 156-162. Lee, Y. S., Cha, B. Y., Saito, K., Yamakawa, H., Choi, S. S., Yamaguchi, K., Yonezawa, T., Teruya, T., Nagai, K., & Woo, J. T. (2010). Nobiletin improves hyperglycemia and insulin resistance in obese diabetic ob/ob mice. Biochemical Pharmacology, 79, 1674-1683. Lefebvre, P., Cariou, B., Lien, F., Kuipers, F., & Staels, B. (2009). Role of bile acids and bile acid receptors in metabolic regulation. Physiological Reviews, 89, 147-191. Legry, V., Francque, S., Haas, J. T., Verrijken, A., Caron, S., Chávez-Talavera, O., Vallez, E., Vonghia, L., Dirinck, E., & Verhaegen, A. (2017). Bile acid alterations are associated with insulin resistance, but not with NASH, in obese subjects. The Journal of Clinical Endocrinology & Metabolism, 102, 3783-3794. Li, Owsley, E., Matozel, M., Hsu, P., Novak, C. M., & Chiang, J. Y. (2010). Transgenic expression of cholesterol 7α‐hydroxylase in the liver prevents high‐fat diet–induced obesity and insulin resistance in mice. Hepatology, 52, 678-690. Li, S., Wang, H., Guo, L., Zhao, H., & Ho, C.-T. (2014). Chemistry and bioactivity of nobiletin and its metabolites. Journal of Functional Foods, 6, 2-10. Li, Y., Tang, R., Leung, P. S., Gershwin, M. E., & Ma, X. (2017). Bile acids and intestinal microbiota in autoimmune cholestatic liver diseases. Autoimmunity Reviews, 16, 885-896. Lioudaki, E., S Ganotakis, E., & P Mikhailidis, D. (2011). Lipid lowering drugs and gallstones: a therapeutic option? Current Pharmaceutical Design, 17, 3622-3631. Liu, L., Dong, W., Wang, S., Zhang, Y., Liu, T., Xie, R., Wang, B., & Cao, H. (2018). Deoxycholic acid disrupts the intestinal mucosal barrier and promotes intestinal tumorigenesis. Food & Function, 9, 5588-5597. Macdonald, I. A., & Roach, P. D. (1981). Bile salt induction of 7α-and 7β-hydroxysteroid dehydrogenases in Clostridium absonum. Biochimica et Biophysica Acta - Lipids and Lipid Metabolism, 665, 262-269. Makishima, M., Okamoto, A. Y., Repa, J. J., Tu, H., Learned, R. M., Luk, A., Hull, M. V., Lustig, K. D., Mangelsdorf, D. J., & Shan, B. (1999). Identification of a nuclear receptor for bile acids. Science, 284, 1362-1365. McClain, C. J., Mokshagundam, S. P. L., Barve, S. S., Song, Z., Hill, D. B., Chen, T., & Deaciuc, I. (2004). Mechanisms of non-alcoholic steatohepatitis. Alcohol, 34, 67-79. Meydani, M., & Hasan, S. T. (2010). Dietary polyphenols and obesity. Nutrients, 2, 737-751. Mi, L. Z., Devarakonda, S., Harp, J. M., Han, Q., Pellicciari, R., Willson, T. M., Khorasanizadeh, S., & Rastinejad, F. (2003). Structural basis for bile acid binding and activation of the nuclear receptor FXR. Molecular Cell, 11, 1093-1100. Morrow, N. M., Telford, D. E., Sutherland, B. G., Edwards, J. Y., & Huff, M. W. (2019). Nobiletin Corrects Intestinal Lipid Metabolism in Ldlr-/-Mice Fed a High-fat Diet. Arteriosclerosis, Thrombosis, and Vascular Biology, 39, A684-A684. Mulvihill, E. E., Assini, J. M., Lee, J. K., Allister, E. M., Sutherland, B. G., Koppes, J. B., Sawyez, C. G., Edwards, J. Y., Telford, D. E., & Charbonneau, A. (2011). Nobiletin attenuates VLDL overproduction, dyslipidemia, and atherosclerosis in mice with diet-induced insulin resistance. Diabetes, 60, 1446-1457. Nakajima, A., Ohizumi, Y., & Yamada, K. (2014). Anti-dementia activity of nobiletin, a citrus flavonoid: A review of animal studies. Clinical Psychopharmacology and Neuroscience, 12, 75. Neuschwander-Tetri, B. A., Loomba, R., Sanyal, A. J., Lavine, J. E., Van Natta, M. L., Abdelmalek, M. F., Chalasani, N., Dasarathy, S., Diehl, A. M., & Hameed, B. (2015). Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. The Lancet, 385, 956-965. Neves, A., Chen, Y., Lê Cao, K. A., Mandal, S., Sharpton, T., McAllister, T., & Guan, L. (2020). Taxonomic and functional assessment using metatranscriptomics reveals the effect of Angus cattle on rumen microbial signatures. Animal, 14, 731-744. Nirogi, R., Goyal, V. K., Jana, S., Pandey, S. K., & Gothi, A. (2014). What suits best for organ weight analysis: review of relationship between organ weight and body/brain weight for rodent toxicity studies. Internatiol Journal of Pharmaceutical Sciences and Research, 5, 1525-1532. Park, M. Y., Kim, S., Ko, E., Ahn, S. H., Seo, H., & Sung, M. K. (2016). Gut microbiota‐associated bile acid deconjugation accelerates hepatic steatosis in ob/ob mice. Journal of Applied Microbiology, 121, 800-810. Parks, D. J., Blanchard, S. G., Bledsoe, R. K., Chandra, G., Consler, T. G., Kliewer, S. A., Stimmel, J. B., Willson, T. M., Zavacki, A. M., & Moore, D. D. (1999). Bile acids: natural ligands for an orphan nuclear receptor. Science, 284, 1365-1368. Pineda Torra, I., Claudel, T., Duval, C., Kosykh, V., Fruchart, J. C., & Staels, B. (2003). Bile acids induce the expression of the human peroxisome proliferator-activated receptor α gene via activation of the farnesoid X receptor. Molecular Endocrinology, 17, 259-272. Portillo-Sanchez, P., Bril, F., & Maximos, M. (2015). High prevalence of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus and normal plasma aminotransferase levels. The Journal of Clinical Endocrinology & Metabolism, 100, 2231-2238. Puri, P., Daita, K., Joyce, A., Mirshahi, F., Santhekadur, P. K., Cazanave, S., Luketic, V. A., Siddiqui, M. S., Boyett, S., & Min, H. K. (2018). The presence and severity of nonalcoholic steatohepatitis is associated with specific changes in circulating bile acids. Hepatology, 67, 534-548. Reaven, G. M. (1988). Role of insulin resistance in human disease. Diabetes, 37, 1595-1607. Ridlon, J. M., Harris, S. C., Bhowmik, S., Kang, D. J., & Hylemon, P. B. (2016). Consequences of bile salt biotransformations by intestinal bacteria. Gut Microbes, 7, 22-39. Ridlon, J. M., Kang, D. J., & Hylemon, P. B. (2006). Bile salt biotransformations by human intestinal bacteria. Journal of Lipid Research, 47, 241-259. Rodrigues, R. R., Gurung, M., Li, Z., García-Jaramillo, M., Greer, R., Gaulke, C., Bauchinger, F., You, H., Pederson, J. W., & Vasquez-Perez, S. (2021). Transkingdom interactions between Lactobacilli and hepatic mitochondria attenuate western diet-induced diabetes. Nature Communications, 12, 1-15. Roma, M. G., Toledo, F. D., Boaglio, A. C., Basiglio, C. L., Crocenzi, F. A., & Sánchez Pozzi, E. J. (2011). Ursodeoxycholic acid in cholestasis: linking action mechanisms to therapeutic applications. Clinical Science, 121, 523-544. Russell, D. W. (2003). The enzymes, regulation, and genetics of bile acid synthesis. Annual Review of Biochemistry, 72, 137. Sayin, S. I., Wahlström, A., Felin, J., Jäntti, S., Marschall, H. U., Bamberg, K., Angelin, B., Hyötyläinen, T., Orešič, M., & Bäckhed, F. (2013). Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metabolism, 17, 225-235. Srivastava, A. (2014). Progressive familial intrahepatic cholestasis. Journal of Clinical and Experimental Hepatology, 4, 25-36. Stofan, M., & Guo, G. L. (2020). Bile acids and FXR: novel targets for liver diseases. Frontiers in Medicine, 7, 544. Stojanov, S., Berlec, A., & Štrukelj, B. (2020). The influence of probiotics on the firmicutes/bacteroidetes ratio in the treatment of obesity and inflammatory bowel disease. Microorganisms, 8, 1715. Sun, T., Chen, M., Shen, H., Fan, L., Chen, X., Wu, J., Xu, Z., & Zhang, J. (2022). Predictive value of LDL/HDL ratio in coronary atherosclerotic heart disease. BMC Cardiovascular Disorders, 22, 1-11. Targher, G., Day, C. P., & Bonora, E. (2010). Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. New England Journal of Medicine, 363, 1341-1350. Thomas, C., Gioiello, A., Noriega, L., Strehle, A., Oury, J., Rizzo, G., Macchiarulo, A., Yamamoto, H., Mataki, C., & Pruzanski, M. (2009). TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metabolism, 10, 167-177. Thomas, C., Pellicciari, R., Pruzanski, M., Auwerx, J., & Schoonjans, K. (2008). Targeting bile-acid signalling for metabolic diseases. Nature Reviews Drug Discovery, 7, 678-693. Vaquero, J., Monte, M. J., Dominguez, M., Muntané, J., & Marin, J. J. (2013). Differential activation of the human farnesoid X receptor depends on the pattern of expressed isoforms and the bile acid pool composition. Biochemical Pharmacology, 86, 926-939. Wahlström, A., Sayin, S. I., Marschall, H. U., & Bäckhed, F. (2016). Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metabolism, 24, 41-50. Wan, F., Han, H., Zhong, R., Wang, M., Tang, S., Zhang, S., Hou, F., Yi, B., & Zhang, H. (2021). Dihydroquercetin supplement alleviates colonic inflammation potentially through improved gut microbiota community in mice. Food & Function, 12, 11420-11434. Wang, H., Chen, J., Hollister, K., Sowers, L. C., & Forman, B. M. (1999). Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. Molecular Cell, 3, 543-553. Watanabe, M., Houten, S. M., Mataki, C., Christoffolete, M. A., Kim, B. W., Sato, H., Messaddeq, N., Harney, J. W., Ezaki, O., & Kodama, T. (2006). Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature, 439, 484-489. Watanabe, M., Houten, S. M., Wang, L., Moschetta, A., Mangelsdorf, D. J., Heyman, R. A., Moore, D. D., & Auwerx, J. (2004). Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. The Journal of Clinical Investigation, 113, 1408-1418. WHO. (1995). Physical status: The use of and interpretation of anthropometry, Report of a WHO Expert Committee: World Health Organization. Wong, Oelkers, P., Craddock, A. L., & Dawson, P. A. (1994). Expression cloning and characterization of the hamster ileal sodium-dependent bile acid transporter. Journal of Biological Chemistry, 269, 1340-1347. Wong, Tse, C. H., Lam, T. Y., Wong, L. H., Chim, M. L., Chu, C. W., Yeung, K. W., Law, T. W., Kwan, H. S., & Yu, J. (2013). Molecular characterization of the fecal microbiota in patients with nonalcoholic steatohepatitis–a longitudinal study. PloS One, 8, e62885. Xiang, J., Zhang, Z., Xie, H., Zhang, C., Bai, Y., Cao, H., Che, Q., Guo, J., & Su, Z. (2021). Effect of different bile acids on the intestine through enterohepatic circulation based on FXR. Gut Microbes, 13, 1949095. Xu, Li, Y., Meng, X., Zhou, T., Zhou, Y., Zheng, J., Zhang, J.-J., & Li, H.-B. (2017). Natural antioxidants in foods and medicinal plants: Extraction, assessment and resources. International Journal of Molecular Sciences, 18, 96. Xu, H., & Wang, L. (2021). The role of notch signaling pathway in non-alcoholic fatty liver disease. Frontiers in Molecular Biosciences, 8, 792667. Yao, Y., Yan, L., Chen, H., Wu, N., Wang, W., & Wang, D. (2020). Cyclocarya paliurus polysaccharides alleviate type 2 diabetic symptoms by modulating gut microbiota and short-chain fatty acids. Phytomedicine, 77, 153268. Ye, X., Liu, Y., Hu, J., Gao, Y., Ma, Y., & Wen, D. (2021). Chlorogenic acid-induced gut microbiota improves metabolic endotoxemia. Frontiers in Endocrinology, 12, 762691. Younossi, Z. M., Blissett, D., Blissett, R., Henry, L., Stepanova, M., Younossi, Y., Racila, A., Hunt, S., & Beckerman, R. (2016). The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe. Hepatology, 64, 1577-1586. Younossi, Z. M., Koenig, A. B., Abdelatif, D., Fazel, Y., Henry, L., & Wymer, M. (2016). Global epidemiology of nonalcoholic fatty liver disease—meta‐analytic assessment of prevalence, incidence, and outcomes. Hepatology, 64, 73-84. Zeinali, M., Rezaee, S. A., & Hosseinzadeh, H. (2017). An overview on immunoregulatory and anti-inflammatory properties of chrysin and flavonoids substances. Biomedicine and Pharmacotherapy, 92, 998-1009. Zhang, M., Zhang, X., Zhu, J., Zhao, D.-G., Ma, Y.-Y., Li, D., Ho, C.-T., & Huang, Q. (2021). Bidirectional interaction of nobiletin and gut microbiota in mice fed with a high-fat diet. Food & Function, 12, 3516-3526. Zhang, Y., Lee, F. Y., Barrera, G., Lee, H., Vales, C., Gonzalez, F. J., Willson, T. M., & Edwards, P. A. (2006). Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice. Proceedings of the National Academy of Sciences, 103, 1006-1011. Zhang, Y., Limaye, P. B., Renaud, H. J., & Klaassen, C. D. (2014). Effect of various antibiotics on modulation of intestinal microbiota and bile acid profile in mice. Toxicology and Applied Pharmacology, 277, 138-145. Zollner, G., & Trauner, M. (2008). Mechanisms of cholestasis. Clinics in Liver Disease, 12, 1-26. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/83476 | - |
| dc.description.abstract | 肥胖會導致肝臟脂質堆積，而在沒有大量飲酒的情況下肝臟脂肪堆積程度大於肝臟面積的 5% 時，稱為非酒精性脂肪肝 (Non-alcoholic fatty liver disease, NAFLD)。目前 NAFLD 的潛在機制仍未完全明瞭，因為其致病機制是複雜和多因素的，而肥胖所造成的肝損傷、發炎反應、腸道菌相及膽酸平衡的失調，皆可能影響 NAFLD 的疾病進程，研究證明高脂飲食會影響腸道菌相和膽酸代謝，並影響腸肝循環中法尼醇 X 受體 (FXR) 的表現量，導致膽酸及脂質形成的失衡，使堆積於肝臟中的脂肪增加且血清中的膽固醇含量也有所提升，從而增加形成 NAFLD 之風險。因此有研究認為，串聯著腸道及肝臟之間的腸肝循環機制，可能為延緩 NAFLD 的重要討論方向；腸肝循環是指腸道及其微生物群和肝臟之間，藉由肝門靜脈所建立的雙向關係，肝門靜脈能夠將腸道的膽酸及成纖維細胞生長因子 15/19 (FGF15/19) 運輸到肝臟，並與肝臟中的成纖維細胞生長因子受體 4 (FGFR4) 結合，進而調節肝臟中膽固醇 7α 羥化酶 (CYP7A1) 和 FXR 蛋白質表現量的變化，從而影響肝臟中膽固醇的代謝及脂質的形成，因此腸肝循環中腸道菌群、膽酸及 FXR-FGF15 訊號影響著整個循環，也是本次實驗探討 NAFLD 疾病進程的研究目標。
川陳皮素 (Nobiletin) 為存在於柑橘類水果皮中的多甲氧基黃酮化合物，先前的研究顯示其在調節腸道菌相、抗肥胖等作用上具有一定功效；然而其能否藉由腸肝循環及膽酸代謝的變化下影響肝臟之狀態仍未知；因此本研究探討以60% 高脂飲食誘導小鼠非酒精性脂肪肝的模式下，同時以管餵的方式給予低劑量 (20 mg/kg BW) 及高劑量 (100 mg/kg BW) 之川陳皮素，評估其改善 NAFLD 的效果。實驗結果顯示，川陳皮素可以減緩高脂飲食誘導之小鼠體重上升、減少肝臟器官重量、以及減少血液中的膽固醇、三酸甘油酯、低密度脂蛋白以及血糖濃度。於肝臟組織切片染色結果顯示，川陳皮素具有抑制肝臟脂質蓄積的能力，使其脂肪的體積明顯較高脂飲食組小。西方墨點法結果顯示，川陳皮素可以通過調節 FXR-FGF15 路徑，提升肝臟 CYP7A1 蛋白質表現量，從而降低肝臟膽固醇的形成，此外，川陳皮素也可以降低肝臟中的 SREBP-1c 和 FASN 蛋白質表現量，進而減少脂質堆積於肝臟中。在腸道菌群與膽酸分析結果方面，高脂飲食使迴腸膽酸量有所增加，而隨著川陳皮素的介入後，迴腸中能夠活化 FXR 的膽酸含量皆有所下調，而能夠抑制 FXR 的膽酸 (如 αMCA) 含量則上升，其結果可能解釋了川陳皮素使迴腸 FXR 蛋白表現量下降的原因，從而影響腸肝循環並因此調節了肝臟膽酸的形成。16S rRNA 基因序列數據顯示，川陳皮素改變腸道菌群的組成，增加 Akkermansia、Oscillibacter 及 Romboutsia 菌屬的數量和降低 F/B ratio，顯示餵食川陳皮素後能夠調節高脂飲食造成之腸道菌相的失衡並增加益菌之生長。相關性結果顯示 高脂飲食的組別中 Lactobacillus johnsonii、Ligilactobacillus murinus、Anaerostipes hadrus 與膽酸 TCDCA 具正相關性，高劑量川陳皮素的組別中 Dubosiella newyorkensis 與膽酸 UDCA 和 LCA 具正相關；Kineothrix alysoides 與膽酸 DCA 具正相關性，顯示川陳皮素影響高脂飲食小鼠的腸道菌群與膽酸的變化中具潛在相關性的結果，而相關文獻中尚未有研究探討這些菌群和膽酸間的代謝變化關係，因此能藉由本實驗之結果，為潛在影響膽酸變化的腸道菌群提供新的研究方向，也能夠更全面的推論攝取川陳皮素後所影響的腸道菌群、膽酸的變化與腸肝循環機制間的關係，顯示川陳皮素可以調節因高脂飲食引起的腸道菌相失衡，並透過調節膽酸來影響腸肝循環中的下游蛋白質 FXR 表現，從而達到預防非酒精性脂肪肝的進展。 綜合上述結果川陳皮素可以通過改變腸道菌相進而影響膽酸代謝，且藉由腸肝循環使得肝臟 CYP7A1 蛋白質表現量的上升從而降低肝臟膽固醇的含量，此外也降低肝臟 SREBP-1c 和 FASN 的蛋白質表現量，從而減少肝臟的脂肪堆積，最終改善 NAFLD 的疾病進展。 | zh_TW |
| dc.description.abstract | Obesity would lead to the accumulation of lipids in the liver, and when the degree of hepatic steatosis was greater than 5% of the liver area without heavy alcohol consumption, it was called non-alcoholic fatty liver disease (NAFLD).
The pathogenesis of NAFLD has not been fully understood because the underlying mechanisms were complex and multifactorial. Studies have shown that high-fat diet may affect gut bacteria, thereby influencing bile acid metabolism and the protein expression of farnesoid X receptor (FXR) in the enterohepatic circulation. It would lead to serum triglyceride and cholesterol level increase and contribute to the progression of NAFLD. Enterohepatic circulation referred to the bidirectional relationship between liver, gut and its microbiota. This interaction was established by the hepatic portal vein which transported bile acids and Fibroblast growth factor 15/19 (FGF15/19) to the liver and bind to Fibroblast growth factor receptor 4 (FGFR4), thereby influencing Cholesterol 7 alpha-hydroxylase (CYP7A1) and FXR protein expression in liver which regulated the metabolism of cholesterol and the formation of lipids. Nobiletin was a non-polar polymethoxylated flavone found in the citrus peel. In previous studies, it had exhibited significant biological activity, including anti-inflammatory and anti-obesity properties. Besides, it was capable of regulating the ratio of Firmicutes and Bacteroidetes genera in the intestinal flora. However, it was still unknown whether it could affect the state of the liver through the regulation of enterohepatic circulation and bile acid. Therefore, our study aimed to explore the interaction between enterohepatic circulation and NAFLD progression with the nobiletin intake in the high-fat-diet animal model. The results showed that nobiletin could reduce body weight and the total triacylglyceride level in the liver in high-fat diet feeding mice. In addition, the section staining results showed that nobiletin had the ability to inhibit the accumulation of lipids in the liver so that the formation volume of fat droplets was significantly smaller than the high-fat diet group. Nobiletin also had the effect of lowering low density lipoprotein cholesterol (LDL), triacylglyceride and glucose levels in the blood, showing the potential effect of improving fatty liver. Data of immune-blotting further showed that nobiletin could improve bile acid homeostasis through FXR-FGF15 pathway and upregulated CYP7A1 protein levels. Nobiletin could also downregulate SREBP-1c and FASN protein expressions which were related to lipid synthesis in liver. In terms of bile acid analysis results, the high-fat diet would increase the content of bile acid with FXR agonist function, while nobiletin intake would reduce these bile acid, thereby downregulating FXR protein expression in ileum. The 16S rRNA gene sequence data indicated that nobiletin could increase the number of Dubosiella, Oscillibacte, Romboutsia and Akkermensia genera in the intestinal bacteria. In the correlation analysis chart, it showed that Lactobacillus johnsonii, Ligilactobacillus murinus, Anaerostipes hadrus, Dubosiella newyorkensis and Kineothrix alysoides were correlated with taurochenodeoxycholic acid (TCDCA), Ursodeoxycholic acid (UDCA), Lithocholic acid (LCA) and Deoxycholic acid (DCA). These results showed that these bacterial genera may have the ability to influence bile acid conversion. In conclusion, our study showed that nobiletin could affect gut microbiota composition which may potentially influence TCDCA, UDCA, LCA and DCA bile acid metabolism. Besides, nobiletin could also ameliorate NAFLD progression by reducing cholesterol and triglycerides level in liver through regulating CYP7A1, SREBP-1c and FASN protein expression in enterohepatic circulation. | en |
| dc.description.provenance | Made available in DSpace on 2023-03-19T21:08:29Z (GMT). No. of bitstreams: 1 U0001-0709202213364700.pdf: 4424264 bytes, checksum: a487d24616f2ed486a643a28c6dc013e (MD5) Previous issue date: 2022 | en |
| dc.description.tableofcontents | 口試委員會審定書 I
謝誌 II 中文摘要 V Abstract VII 目錄 X 附圖目錄 XIII 附表目錄 XIV 圖目錄 XV 表目錄 XVI 縮寫表 XVII 第一章、 文獻回顧 1 第一節、 非酒精性脂肪肝 (NAFLD) 1 (一) 簡介 1 (二) 定義 2 (三) NAFLD 與肥胖之關係 2 (四) 疾病進程 4 (五) 腸道菌群與肝臟 6 第二節、 腸肝循環 7 (一) 簡介 7 (二) 膽酸合成的經典和替代途徑 8 (三) 代謝調節中的膽酸信號 11 (四) 膽酸與腸道菌群的關係 14 (五) 高脂飲食與腸肝循環間的關係 15 第三節、 川陳皮素 (Nobiletin) 16 (一) 簡介 16 (二) 相關功效背景 17 第二章、 實驗目的與研究架構 19 第一節、 研究目的 19 第二節、 實驗架構 19 第三章、 材料與方法 21 第一節、 實驗材料 21 (一) 儀器與設備 21 (二) 藥品與試劑 22 (三) 抗體 23 (四) 分析套組 24 (五) 樣品來源 24 第二節、動物實驗 (in vivo) 方法 25 (一) 動物品系及飼養環境 25 (二) 空腹血糖測試 28 (三) 胰島素含量測定 28 (四) 動物犧牲 29 (五) 組織切片染色 31 (六) 肝臟三酸甘油酯萃取及定量 34 (七) 組織均質及蛋白質萃取 36 (八) 蛋白質定量 37 (九) 西方墨點法 39 (十) 糞便DNA萃取 44 (十一) 16S rRNA 基因定序及分析 45 (十二) 膽酸含量分析 47 (十三) 統計分析 48 第四章、 結果與討論 49 (一) Nobiletin對餵食高脂飲食 C57BL/6 小鼠外觀及體重之影響 49 (二) Nobiletin對餵食高脂飲食 C57BL/6 小鼠攝食量之影響 52 (三) Nobiletin對餵食高脂飲食 C57BL/6 小鼠臟器外觀及重量之影響 55 (四) Nobiletin對餵食高脂飲食 C57BL/6 小鼠肝臟組織切片染色及脂肪含量之影響 57 (五) Nobiletin對餵食高脂飲食 C57BL/6 小鼠血清生化值之影響 60 (六) Nobiletin對餵食高脂飲食 C57BL/6 小鼠胰島素濃度之影響 63 (七) Nobiletin對餵食高脂飲食 C57BL/6 小鼠腸道膽酸之影響 65 (八) Nobiletin 對餵食高脂飲食 C57BL/6 小鼠腸道菌相組成 68 (九) Nobiletin 對餵食高脂飲食 C57BL/6 小鼠腸道菌相與膽酸相關性預測 76 (十) Nobiletin對餵食高脂飲食 C57BL/6 小鼠迴腸 FXR-FGF15之影響 80 (十一) Nobiletin對餵食高脂飲食 C57BL/6 小鼠肝臟 CYP7A1 之影響 82 (十二) Nobiletin對餵食高脂飲食 C57BL/6 小鼠肝臟脂肪生成反應之影響 85 第五章、 結論 89 第六章、 參考文獻 91 第七章、 附錄 102 | - |
| dc.language.iso | zh_TW | - |
| dc.title | 川陳皮素通過調節腸肝循環改善高脂飲食誘導非酒精性脂肪肝的作用 | zh_TW |
| dc.title | Effect of nobiletin on improving high-fat diet-induced non-alcoholic fatty liver disease by regulating enterohepatic circulation | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 110-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 黃步敏;王應然;廖秀娟;何元順 | zh_TW |
| dc.contributor.oralexamcommittee | BU-MIN HUANG;YING-RAN WANG;XIU-JUAN LIAO;YUAN-SHUN HE | en |
| dc.subject.keyword | 非酒精性脂肪肝,腸肝循環,FXR,腸道菌相,川陳皮素, | zh_TW |
| dc.subject.keyword | NAFLD,Enterohepatic circulation,FXR,Gut microbiota,Nobiletin, | en |
| dc.relation.page | 102 | - |
| dc.identifier.doi | 10.6342/NTU202203220 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2022-09-08 | - |
| dc.contributor.author-college | 生物資源暨農學院 | - |
| dc.contributor.author-dept | 食品科技研究所 | - |
| 顯示於系所單位： | 食品科技研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-110-2.pdf 目前未授權公開取用 | 4.32 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。