55
Alwan, A. (2011) Global status report on noncommunicable diseases 2010. World Health Organization.
Andres-Hernando, A., Johnson, RJ., Lanaspa, MA. (2019) Endogenous fructose production: what do we know
and how relevant is it? Current Opinion in Clinical Nutrition & Metabolic Care. 22; 289-294. doi:
10.1097/MCO.0000000000000573.
Arita, Y., Kihara, S., Ouchi, N., Takahashi, M., Maeda, K., Miyagawa, J., Hotta, K., Shimomura, I.,
Nakamura, T., Miyaoka, K., Kuriyama, H., Nishida, M., Yamashita, S., Okubo, K., Matsubara, K.,
Muraguchi, M., Ohmoto, Y., Funahashi, T., Matsuzawa. Y. (1999) Paradoxical decrease of an
adipose-specific protein, adiponectin, in obesity. Biochemical Biophysical Research Communications.
257; 79-83. doi: 10.1006/bbrc.1999.0255.
Becker, BD., Borghi C., Burnier, M., Borne P. (2019) Uric acid and hypertension: a focused review and
practical recommendations. Journal of Hypertension. 37; 878-883.
doi:10.1097/HJH.0000000000001980.
Bertaggia, E., Jensen., KK., Castro-Perez, J., Xu., Paolo. GD., Chan, RB., Wang L., Haeusler., RA. (2017)
Cyp8b1 ablation prevents Western diet-induced weight gain and hepatic steatosis because of impaired
fat absorption. Journal of Physiology Endocrinol and Metabolism. 313; E121-E133. doi:
10.1152/ajpendo.00409.
Bitter, A., Nüssler, AK., Thasler, WE., Klein, K., Zanger, UM., Schwab, M., Burk, O. (2015) Human sterol
regulatory element-binding protein 1a contributes significantly to hepatic lipogenic gene expression.
Cellular Physiology and Biochemistry. 35; 803-15. doi: 10.1159/000369739.
Bloch, K., Berg, BN., Rittenberg, D. (1943) The biological conversion of cholesterol to cholic acid. Journal of
Biological Chemistry, 149; 511-517.
Brown, G.C. (2015) Living too long: The current focus of medical research on increasing the quantity, rather
than the quality, of life is damaging our health and harming the economy. EMBO Report. 16; 137–
141.
56
Caussy, C., Hsu, C., Singh, S., Bassirian, S., Kolar, J., Faulkner, C., Sinha, N., Bettencourt, R., Gara, N.,
Valasek, MA., Schnabl, B., Richards, L., Brenner, DA., Hofmann, AF., Loomba, R. (2019) Serum
bile acid patterns are associated with the presence of NAFLD in twins, and dose-dependent changes
with increase in fibrosis stage in patients with biopsy-proven NAFLD. Alimentary Pharmacology &
Therapeutics. 49(2); 183-193.
Chiang, J.Y.L. (2009) Bile acids: regulation of synthesis. Journal of Lipid Research. 50(10); 1955–1966.
Do, MH., Lee, E., Oh, MJ., Kim, Y., Park, HY. (2018) High-Glucose or -Fructose Diet Cause Changes of the
Gut Microbiota and Metabolic Disorders in Mice without Body Weight Change. Nutrients. 10(6); 761.
doi: 10.3390/nu10060761.
Dulai, PS., Singh, S., Patel, J., Soni, M., Prokop, LJ., Younossi, Z,m Sebastiani, G., Ekstedt, M., Hagstrom,
H., Nasr, P., Stal, P., Wong, VW., Kechagias, S., Hultcrantz, R., Loombaet, R. (2017) Increased risk
of mortality by fibrosis stage in nonalcoholic fatty liver disease: systematic review and meta-analysis.
Hepatology. 65(5); 1557–65.
Eslam, M., Newsome, PN., Sarin, SK., Anstee, QM., Targher, G., Romero-Gomez, M., Zelber-Sagi, S.,
Wong, VW., Dufour, JF., Schattenberg, JM., Kawaguchi, K., Arrese, M., Valenti, L., Shiha, G.,
Tiribelli, C., Yki-Järvinen, H., Fan, DJ., Grønbæk, H., Yilmaz, Y, Cortez-Pinto, H., Oliveira, CP.,
Bedossa, P., Adams, LA., Zheng, MH., Fouad, Y., Chan, WK., Mendez-Sanchez, N., Ahn, SH.,
Castera, L., Bugianesi, E., Ratziu, V., George, J. (2020) A new definition for metabolic dysfunctionassociated fatty liver disease: an international expert consensus statement. Journal of Hepatology. 73;
202-209. doi: 10.1016/j.jhep.2020.03.039.
Febbraio, MA., Reibe, S., Shalapour, S., Ooi, GJ., Watt, MJ., and Karin, M. (2019) Preclinical models for
studying NASH-driven HCC: How useful are they? Cell Metabolism. 29; 18-26.
Felig, P., Owen, OE., Wahren, J., and Cahill, GF. Jr. (1969) Amino acid metabolism during prolonged
starvation. Journal of Clinical Investigation. 48; 584-594.
57
Festing, M.F.W. (1997) Variation and its implications for the design of experiments in toxicological research.
Comparative Hematology International. 7; 202–207.
Festing, M.F.W. (2010) Inbred strains should replace outbred stocks in toxicology, safety testing, and drug
development. Toxicologic Pathology. 38; 681–690.
Festing, M.F.W. (2014) Evidence should trump intuition by preferring inbred strains to outbred stocks in
preclinical research. Journal of the Institute for Laboratory Animal Research. 55; 399-404.
Folch, J., Lees, M., Sloane Stanley, GH. (1957) A simple method for the isolation and purification of total
lipides from animal tissues. Journal of Biological Chemistry. 226; 497-509. doi: 10.1016/S00219258(18)64849-5.
Ghebreyesus, TA. (2022) Global status report on physical activity 2022. World Health Organization.
Gill, TJ. (1980) The use of randomly bred and genetically defined animals in biomedical research. The
American Journal of Pathology. 101; S21–32.
Haeusler, RA, Pratt-Hyatt, M, Welch, CL, Klaassen, CD, Accili D. (2012) Impaired generation of 12hydroxylated bile acids links hepatic insulin signaling with dyslipidemia. Cell Metabolism. 15; 65-74.
Haeusler, RA., Astiarraga, B., Camastra, S., Accili, D., Ferrannini, E. (2013) Human insulin resistance is
associated with increased plasma levels of 12α-hydroxylated bile acids. Diabetes. 62; 4184-4191. doi:
10.2337/db13-0639.
Hagio, M., Matsumoto, M., Fukushima, M., Hara, H., Ishizuka, S. (2009) Improved analysis of bile acids in
tissues and intestinal contents of rats using LC/ESI-MS. Journal of Lipid Research. 50; 173-180. doi:
10.1194/jlr.D800041-JLR200.
Hofmann, A. F., & Mysels, K. J. (1988) Bile salts as biological surfactants. Colloids and Surfaces, 30(1);
145–173.
Hori, S., Hara, H., Ishizuka, S. (2018) Marginal iron deficiency enhances liver triglyceride accumulation in
rats fed a high-sucrose diet. Bioscience, Biotechnology, and Biochemistry. 82; 2140-2148. doi:
10.1080/09168451.2018.1515616.
58
Hori, S., Abe, T., Lee, DG., Fukiya, S., Yokota, A., Aso, N., Shirouchi, B., Sato, M., Ishizuka, S. (2020)
Association between 12α-hydroxylated bile acids and hepatic steatosis in rats fed a high-fat diet.
Journal of Nutritional Biochemistry. 83; 108412. doi: 10.1016/j.jnutbio.2020.108412.
Hori, S., Liu, H., Yamada, R., Ichitsubo, S., Sakaguchi, A., Yokoyama, F., Ishizuka, S. (2022) Extraction of
bile acids from biological samples and quantification using ultra high-performance liquid
chromatography-orbitrap mass spectrometry, In C.B.B. Cazarin (Ed.), Basic Protocols in Foods and
Nutrition, Humana Press, p.115-127, doi: 10.1007/978-1-0716-2345-9_8.
Hundal, RS., Petersen, KF., Mayerson, AB., Randhawa, PS., Inzucchi, S., Shoelson, SE., and Shulman, GI.
(2002) Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes.
Journal of Clinical Investigation. 109; 1321-1326.
Ibrahim, SH., Hirsova, P., Malhi, H., Gores, GJ. (2016) Animal Models of Nonalcoholic Steatohepatitis: Eat,
Delete, and Inflame. Digestive Diseases and Sciences. 61; 1325-1336.
Islam, KMBS., Fukiya, S., Hagio, M., Fujii, N., Ishizuka, S., Ooka, T., Ogura, Y., Hayashi, T., Yokota, A.
(2011) Bile acid is a host factor that regulates the composition of the cecal microbiota in rats.
Gastroenterology. 141; 1773-1781. doi: 10.1053/j.gastro.2011.07.046.
Jalal, DI., Smits, G., Johnson, RJ., Chonchol. M. (2010) Increased fructose associates with elevated blood
pressure. Journal of the American Society of Nephrology. 21; 1543-1549. doi:
10.1681/ASN.2009111111. 20.
Karpe, F. (1999) Postprandial lipoprotein metabolism and atherosclerosis. Journal of International Medicine.
246; 341–355.
Kitagawa, E, Yamamoto, T, Yamamoto, K, Nakagawa, T, Hayakawa, T. (2015) Accumulation of lipid in rat
liver was induced by vitamin B6 deficiency and was ameliorated by supplemental
phosphatidylcholine in the diet. Bioscience, Biotechnology, and Biochemistry, 79(8); 1320–1326.
Kleinert, M., Clemmensen, C., Hofmann, SM., Moore, MC., Renner, S., Woods, SC., Huypens, P., Beckers,
J., de Angelis, MH., Schürmann, A., Bakhti, M., Klingenspor, M., Heiman, M., Cherrington, AD.,
59
Ristow, M., Lickert, H., Wolf, E., Havel, PJ., Müller, TD., and Tschöp, MH. (2018) Animal models of
obesity and diabetes mellitus. Nature Reviews Endocrinology. 14; 140-162.
Kobayashi, K., Sakuratani, Y., Abe, T., Yamazaki, K., Nishikawa, S., Yamada, J., Hirose, A., Kamata, E., and
Hayashi, M. (2011) Influence of coefficient of variation in determining significant difference of
quantitative values obtained from 28-day repeated-dose toxicity studies in rats. Journal of
Toxicological Sciences. 36; 63-71.
Konarzewski, M., and Diamond, J. (1995) Evolution of basal metabolic rate and organ masses in laboratory
mice. Evolution. 49; 1239-1248.
Krasowski, MD., Yasuda, K., Hagey, LR., Schuetz, EG. (2005) Evolution of the pregnane x receptor:
adaptation to cross-species differences in biliary bile salts. Molecular Endocrinology. 19; 1720-1739.
doi: 10.1210/me.2004-0427.
Kumagai, H., Oshima, N., Matsuura, T., Imai, M., Iigaya, K., Onimaru, H., Kawai, A., Sakata, K., Onami, T.,
Takimoto, C., Kamayachi, T., Osaka, M., Hayashi, K., Itoh, H., Saruta, T. (2007) Whole-cell patchclamp and optical imaging of neurons in the RVLM, the CVLM, and the caudal end of VLM. In:
Kubo T, Kuwaki T (eds). Central Mechanisms of Cardiovascular Regulation. Transworld Research
Network, Kerala, India, p. 83-106.
Kumagai, H., Oshima, N., Matsuura, T., Iigaya,K., Imai, M., Onimaru, H., Sakata, K., Osaka, M., Onami, T,
Takimoto, C., Kamayachi, T., Itoh, H., Saruta, T. (2012) Importance of rostral ventrolateral medulla
neurons in determining efferent sympathetic nerve activity and blood pressure. Hypertension
Research. 35(2); 132-141. doi: 10.1038/hr.2011.208.
Lanaspa, MA., Ishimoto, T., Li, N., Cicerchi, C., Orlicky, DJ., Ruzycki, P., Rivard, C., Inaba, S., RoncalJimenez, CA., Bales, ES., Diggle, CP., Asipu, A., Petrash, JM., Kosugi, T., Maruyama, S., SanchezLozada, LG., McManaman, JL., Bonthron, DT., Sautin, YY., Johnson, RJ. (2013) Endogenous
fructose production and metabolism in the liver contributes to the development of metabolic
syndrome. Nature Communications. 4; 2434. doi: 10.1038/ncomms3434.
60
Lee, Y., Yoshitsugu, R., Kikuchi, K., Joe, GH., Tsuji, M., Nose, T., Shimizu, H., Hara, H., Minamida, K.,
Miwa, K., and Ishizuka, S. (2016) Combination of soya pulp and Bacillus coagulans lilac-01 improves
intestinal bile acid metabolism without impairing the effects of prebiotics in rats fed a cholic acidsupplemented diet. British Journal of Nutrition. 116; 603-610.
Lee, JY., Shimizu, H., Hagio, M., Fukiya, S., Watanabe, M., Tanaka, Y., Joe, GH., Iwaya, H., Yoshitsugu, R.,
Kikuchi, K., Tsuji, M., Baba, N., Nose, T., Tada, K., Hanai, T., Hori, S., Takeuchi, A., Furukawa, Y.,
Shirouchi, B., Sato, M., Ooka, T., Ogura, Y., Hayashi, T., Yokota, A., Ishizuka, S. (2020) 12αHydroxylated bile acid induces hepatic steatosis with dysbiosis in rats. Biochimica et Biophysica Acta
- Molecular and Cell Biology of Lipids. 1865; 158811. doi: 10.1016/j.bbalip.2020.158811.
Lee, H., Lee, YH., Kim, SU., Kim, HC., (2021) Metabolic dysfunction-associated fatty liver disease and
incident cardiovascular disease risk: a nationwide cohort study. Clinical Gastroenterology and
Hepatology. 19; 2138-2147. doi: 10.1016/j.cgh.2020.12.022.
Li, J., Zou, B., Yeo YH, Feng, Y., Xie, X., Lee, DH., Fujii, H., Wu, Y., Kam, LY., Ji, F., Li, X., Chien, N.,
Wei, M., Ogawa, E., Zhao, C., Wu, X., Stave, CD., Henry, L., Barnett, S., Takahashi, H., Furusyo, N.,
Eguchi, Y., Hsu, YC., Lee, TY., Ren, W., Qin, C., Jun, DW., Toyoda, H., Wong, VW., Cheung, R.,
Zhu, Q., Nguyenl, MH., (2019) Prevalence, incidence, and outcome of non-alcoholic fatty liver
disease in Asia,1999–2019: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 4
(5); 389–98.
Lin, Y., Havinga, R., Verkade, HJ., Moshage, H., Slooff, MJ., Vonk, RJ., Kuipers F. (1996) Bile acids
suppress the secretion of very-low-density lipoprotein by human hepatocytes in primary culture.
Hepatology, 23(2); 218-228.
Maithilikarpagaselvi, N., Sridhar, MG., Swaminathan., RP., Sripradha, R., Badhe, B. (2016) Curcumin
inhibits hyperlipidemia and hepatic fat accumulation in high-fructose-fed male Wistar rats.
Pharmaceutical Biology. 54(12); 2857-2863. doi: 10.1080/13880209.2016.1187179.
61
Medina, P., Silvente-Poirot, S., Poirot, M. (2022) Oxysterols are potential physiological regulators of ageing.
Ageing Research Reviews. 77; 101615. doi: 10.1016/j.arr.2022.101615.
Minegishi, S., Luft, FC., Titze, J., Kitada, K. (2020) Sodium Handling and Interaction in Numerous Organs.
American Journal of Hypertension. 33(8); 687–694. doi: 10.1093/ajh/hpaa049.
Moghadasian, MH., Frohlich, JJ. (1999) Effects of dietary phytosterols on cholesterol metabolism and
atherosclerosis: clinical and experimental evidence. American Journal of Medicine. 107(6); 588-594.
doi: 10.1016/s0002-9343(99)00285-5.
Myant, N. B., & Mitropoulos, K. A. (1977) Cholesterol 7α-hydroxylase. Journal of Lipid Research. 18; 135–
153.
Nakayama, T., Kosugi, T., Gersch, M., Connor, T., Sanchez-Lozada, LG., Lanaspa, MA., Roncal, C, PerezPozo,SE., Johnson, RJ., Nakagawa, T. (2010) Dietary fructose causes tubulointerstitial injury in the
normal rat kidney. American Journal of Physiology Renal Physiology. 298(3); F712-720. doi:
10.1152/ajprenal.00433.
Nimer, N., Choucair, I., Wang, Z., Nemet, I., Lim L., Gukasyan, J., Weeks, TL., Alkhouri, N., Zein, N., Tang,
W.H.W., Fischbach, MA., Brown, JM., Allayee, H., Dasarathy, S., Gogonea, V., Hazen, SL. (2021)
Bile acids profile, histopathological indices and genetic variants for non-alcoholic fatty liver disease
progression. Metabolism. 116; 154457. doi: 10.1016/j.metabol.2020.154457.
Nishiyama, A. (2019) Pathophysiological mechanisms of mineralocorticoid receptor-dependent
cardiovascular and chronic kidney disease. Hypertensions research. 42(3); 293-300. doi:
10.1038/s41440-018-0158-6.
Nolop, KB., Rhodes, CG., Brudin, LH., Beaney, RP., Krausz, T., Jones, T., Hughes, J.M.B. (1987) Glucose
utilization in vivo by human pulmonary neoplasms. Cancer. 60; 2682-2689.
Osada, K., Hoshina, S., Nakamura, S., Sugano, M. (2000) Cholesterol oxidation in meat products and its
regulation by supplementation of sodium nitrite and apple polyphenol before processing. Journal of
Agricultural and Food Chemistry. 48; 3823-3829. doi: 10.1021/jf991187k.
62
Oude Griep, LM., Seferidi, P., Stamler, J., Van Horn, L., Chan, Q., Tzoulaki, I, Steffen, LM., Miura, K.,
Ueshima, H., Okuda, N., Zhao, L., Soedamah-Muthu, SS., Daviglus, ML., Elliott P. (2016)
INTERMAP Research Group, Relation of unprocessed, processed red meat and poultry consumption
to blood pressure in East Asian and Western adults. Journal of Hypertension. 34; 1721-1729. doi:
10.1097/HJH.0000000000001008.
Pandak, WM., Bohdan, P., Franklund, C., Mallonee, DH., Eggertsen, G., Björkhem, I., Gil, G., Vlahcevic,
ZR., Hylemon, PB. (2001) Expression of sterol 12α-hydroxylase alters bile acid pool composition in
primary rat hepatocytes and in vivo. Gastroenterology, 120(7); 1801–1809.
Pathak, P., Chiang, John Y L. (2019) Sterol 12α-Hydroxylase Aggravates Dyslipidemia by Activating the
Ceramide/mTORC1/SREBP-1C Pathway via FGF21 and FGF15. Gene Expression the Journal of
Liver Research, 19; 161-173.
Rahunen, R., Kummu, O., Koivukangas, V., Hautajärvi, H., Hakkola, J., Rysä, J., Hukkanen, J. (2022)
Pregnane X receptor‒4β-hydroxycholesterol axis in the regulation of overweight- and obesity-induced
hypertension. Journal of the American Heart Association. 11; e023492. doi:
10.1161/JAHA.121.023492.
Reeves, PG., Nielsen, FH., Fahey GC. (1993) AIN-93 purified diets for laboratory rodents: final report of the
American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent
diet. The Journal of Nutrition. 123; 1939-1951. doi: 10.1093/jn/123.11.1939.
Ridlon, JM., Kang, DJ., Hylemon, PB. (2006) Bile salt biotransformations by human intestinal bacteria.
Journal of Lipid Research, 47(2); 241–259.
Ruggenenti, P, Remuzzi, G. (2006) Time to abandon microalbuminuria? Kidney International. 70; 1214-1222.
doi: 10.1038/sj.ki.5001729.
Schwarz, M., Lund, E. G., Setchell, K. D., Kayden, H. J., Zerwekh, J. E., Björkhem, I., Herz, J., Russell, D.
W. (1996) Disruption of cholesterol 7α-hydroxylase gene in mice. II. Bile acid deficiency is overcome
by induction of oxysterol 7α-hydroxylase. Journal of Biological Chemistry, 271(30); 18024-18031.
63
Semova, I., Levenson, AE., Krawczyk, J., Bullock, K., Gearing, ME., Ling, AV., Williams, KA., Miao, J.,
Adamson, SS., Shin, DJ., Chahar, S., Graham, MJ., Crooke, RM., Hagey, LR., Vicent, D., Ferranti,
SD., Kidambi, S., Clish, CB., Biddinger, SB. (2022) Insulin prevents hypercholesterolemia by
suppressing 12α-hydroxylated bile acids. Circulation. 145; 969-982. doi:
10.1161/CIRCULATIONAHA.120.045373.
Sheng, HW. (2000) Sodium, chloride and potassium. In: Stipanuk M, ed. Biochemical and Physiological
Aspects of Human Nutrition. Philadelphia: W.B. Saunders Company; 686-710.
Shimano, H, Horton, JD., Shimomura, I., Hammer, RE., Brown, MS., Goldstein, JL. (1997) Isoform 1c of
sterol regulatory element binding protein is less active than isoform 1a in livers of transgenic mice and
in cultured cells. Journal of Clinical Investigation. 99; 846-854. doi: 10.1172/JCI119248.
Shimano, H. (2001) Sterol regulatory element-binding proteins (SREBPs): transcriptional regulators of lipid
synthetic genes. Progress in Lipid Research. 40; 439-452.
Shirouchi, B., Kashima, K., Horiuchi, Y., Nakamura, Y., Fujimoto, Y., Tong, LT., Sato, M. (2017) 27Hydroxycholesterol suppresses lipid accumulation by down-regulating lipogenic and adipogenic gene
expression in 3T3-L1 cells. Cytotechnology. 69; 485-492. doi: 10.1007/s10616-016-9962-5.
Terubayashi, H., Sato, S., Nishimura, C., Kador, PF., Kinoshita, JK. (1989) Localization of aldose and
aldehyde reductase in the kidney. Kidney International. 36; 843-51. doi: 10.1038/ki.1989.270.
Tkáč, I., Keene, CD., Pfeuffer, J., Low, WC., and Gruetter, R. (2001) Metabolic changes in quinolinic acidlesioned rat striatum detected non-invasively by in vivo 1H NMR spectroscopy. Journal of
Neuroscience Research. 66; 891-898.
Ueki, K., Sasako, T., Okazaki, Y., Kato, M., Okahata, S., Katsuyama, H., Haraguchi, M., Morita, A., Ohashi,
K., Hara, K., Morise, A., Izumi, K, Ishizuka N., Ohashi Y., Noda M., Kadowaki, T., J-DOIT3 Study
Group. (2017) Effect of an intensified multifactorial intervention on cardiovascular outcomes and
mortality in type 2 diabetes (J-DOIT3): an open-label, randomised controlled trial. Lancet Diabetes
Endocrinology. 5; 951-964.
64
Ugele, B., Kempen, HJ., Kempen, JM., Gebhardt, R., Meijer, P., Burger, HJ., Princen, HM. (1991)
Heterogeneity of rat liver parenchyma in cholesterol 7 alpha-hydroxylase and bile acid synthesis.
Biochemical Journal. 276; 73–77.
Wallace, M., & Metallo, CM. (2020) Tracing insights into de novo lipogenesis in liver and adipose tissues.
Seminars in Cell & Developmental Biology, 108; 65-71.
World Health Organization. (2000) The World health report: 2000: health systems: improving performance.
World Health Organization, Geneve, Switzerland.
World Health Organization. (2022) Global action plan for the prevention and control of noncommunicable
disease 2022-2030 WHO Document Production Services, Geneve, Switzerland.
Yamauchi, T., Kamon, J., Minokoshi, Y., Ito, Y., Waki, H., Uchida, S., Yamashita, S., Noda, M., Kita, S.,
Ueki, K., Eto, K., Akanuma, Y., Froguel, P., Foufelle, F., Ferre, P., Carling, D., Kimura, S., Nagai, R.,
Kahn, BB., Kadowaki T. (2002) Adiponectin stimulates glucose utilization and fatty-acid oxidation by
activating AMP-activated protein kinase. Nature Medicine. 8; 1288-1295. doi: 10.1038/nm788.
Yang, K., Zhang, P., Lv, T., Wu, J., Liu, Q. (2022) Acupuncture at Taichong and Zusanli points exerts
hypotensive effect in spontaneously hypertensive rats by metabolomic analysis. Journal of
Chromatography B. 1207; 123352. doi: 10.1016/j.jchromb.2022.123352.
Ye, Q., Zou, B., Yeo, YH., Li, J., Huang, DQ., Wu, Y., Yang, H., Liu, C., Kam, LY., Tan, W.W.E., Chien, N.,
Trinh, S., Henry, L., Stave, CD., Hosaka, T., Cheung, RC., Nguyen, MH. (2020) Global prevalence,
incidence, and outcomes of non-obese or lean non-alcoholic fatty liver disease: a systematic review
and meta-analysis. Lancet Gastroenterol Hepatology. 5; 739-752. doi: 10.1016/S24681253(20)30077-7.
Younossi, ZM, Koenig, AB, Abdelatif, D, Fazel Y, Henry, L, Wymer, M. (2016) Global epidemiology of
nonalcoholic fatty liver disease̶ meta-analytic assessment of prevalence, incidence, and outcomes.
Hepatology. 64(1); 73–84.
65
Yoshitsugu, R., Kikuchi, K., Iwaya, h., Fujii, N., Hori, S., Lee, DG., Ishizuka, S. (2019) Alteration of bile acid
metabolism by a high-fat diet is associated with plasma transaminase activities and glucose
intolerance in rats. Journal of Nutritional Science and Vitaminology. 65; 45-51. doi:
10.3177/jnsv.65.45.
Yoshitsugu, R., Liu, H, Kamo, Y., Takeuchi, A., Joe, GH., Tada, K., Kikuchi, K., Fujii, N., Kitta, S., Hori, S.,
Takatsuki, M., Iwaya, H., Tanaka, Y., Shimizu, H., Ishizuka, S. (2021) 12α-Hydroxylated bile acid
enhances accumulation of adiponectin and immunoglobulin A in the rat ileum. Scientific Reports. 11;
12939. doi: 10.1038/s41598-021-92302-z.
Young, AA., Gedulin, BR., Bhavsar, S., Bodkin, N., Jodka, C., Hansen, B., Denaro, M. (1999). Glucoselowering and insulin-sensitizing actions of exendin-4: studies in obese diabetic (ob/ob, db/db) mice,
diabetic fatty Zucker rats, and diabetic rhesus monkeys (Macaca mulatta). Diabetes 48; 1026-1034.
Zhang, F., Yuan, W., Wei, Y., Zhang, D., Duan, Y., Li, B., Wang, X., Xi, L., Zhou, Y., Wu, X. (2019) The
alterations of bile acids in rats with high-fat diet/streptozotocin-induced type 2 diabetes and their
negative effects on glucose metabolism. Life Science. 229; 80-92. doi: 10.1016/j.lfs.2019.05.031.
66
参考論文
Shimoda, T., Hori, S., Maegawa, K., Takeuchi, A., Lee, Y., Joe, G., Tanaka, Y., Shimizu, H., Ishizuka, S.
(2020) A low coefficient of variation in hepatic triglyceride concentration in an inbred rat strain. Lipids in
Health and Disease, 19(1), 137.
Shimoda, T., Shimizu, H., Iwasaki, W., Liu, H., Kamo, Y., Tada, K., Hanai, T., Hori, S., Joe, G., Tanaka, Y.,
Sato, M., Miyazaki, H., Ishizuka, S. (2022) A diet supplemented with cholic acid elevates blood pressure
accompanied by albuminuria in rats. Bioscience, Biotechnology, and Biochemistry, in press.
67
国内学会
下田智子,清水英寿,加茂佳恵,多田幸司,花井健人,堀将太,田中愛建,佐藤匡央,石塚敏
ットにおけるコール酸摂取による肝脂質蓄積の増加は血圧の上昇を伴う,日本栄養·食糧学会北海
道支部大会 (2022 年,札幌,口頭発表)
68
謝辞
本論文は数多くの方々の御協力を賜り,作製されたものです.私は,博士後期課程から本研究室
へ入学しました.入学時から学位取得までの 7 年間,細部にわたる御指導と御助言,さらに本論文
の主査として御校閲を賜りました北海道大学大学院農学研究院基盤研究部門生物機能化学分野食品
栄養学研究室の石塚敏教授に心より感謝申し上げます.また, 御多忙にも関わらず副査の御快諾と
御校閲を賜りました食品機能化学研究室の園山慶教授,食品栄養学研究室の比良徹准教授に謹んで
感謝の意を表します.さらに研究全般に関し,御助言,御指導いただいた島根大学大学院自然科学
研究科農生命科学専攻の清水英寿教授に深謝申し上げます.また,筑波大学大学院生命科学環境研
究科宮崎均教授には,血圧測定に際し,機器の提供をしていただきました.九州大学大学院農学研
究院生命機能科学部門食料化学工学講座栄養化学分野の佐藤匡央教授には,肝臓の酸化コレステロ
ール解析をしていただき,研究結果の解釈に際し,多くの御助言,御指導をいただきました.厚く
感謝申し上げます.
在学期間は,胆振東部地震および新型コロナウイルス感染症の流行によりサンプル管理などにお
いて食品栄養学研究室の皆様に筆舌に尽くしがたいほどの御支援をいただきました.また,本研究
を執行するにあたり尊い命をささげてくれたラットの冥福を祈り,全ての皆様に心より御礼申し上
げます.
2023 年 3 月
下田
智子
69
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