| 1. |
Wakana Iwasaki, Ryo Yoshida, Hongxia Liu, Shota Hori, Yuki Otsubo, Yasutake Tanaka, Masao Sato, Satoshi Ishizuka, The ratio of 12α to non-12-hydroxylated bile acids reflects hepatic triacylglycerol accumulation in high-fat diet-fed C57BL/6J mice, Scientific Reports, 10.1038/s41598-022-20838-9, 12, 1, 16707, 2022.10. |
| 2. |
Xingyu Yuan, Rika Nagamine, Yasutake Tanaka, Wei-Ting Tsai, Zhe Jiang, Ai Takeyama, Katsumi Imaizumi, Masao Sato, The effects of dietary linoleic acid on reducing serum cholesterol and atherosclerosis development are nullified by a high-cholesterol diet in male and female apolipoprotein E-deficient mice, British Journal of Nutrition, https://doi.org/10.1017/S0007114522001325, 2022.05. |
| 3. |
Yeonmi Lee, Yasutake Tanaka, Wakana Iwasaki, Fumika Yokoyama, Ga-Hyun Joe, Misaki Tsuji, Takuma Nose, Koji Tada, Taketo Hanai, Shota Hori, Hidehisa Shimizu, Kimiko Minamida, Kazunori Miwa, Satoshi Ishizuka, Dietary supplementation with okara and Bacillus coagulans lilac-01 improves hepatic lipid accumulation induced by cholic acids in rats, Journal of Functional Foods, https://doi.org/10.1016/j.jff.2022.104991, 2022.04. |
| 4. |
Reika Yoshitsugu, Hongxia Liu, Yoshie Kamo, Akari Takeuchi, Ga-Hyun Joe, Koji Tada, Keidai Kikuchi, Nobuyuki Fujii, Shinri Kitta, Shota Hori, Manami Takatsuki, Hitoshi Iwaya, Yasutake Tanaka, Hidehisa Shimizu, Satoshi Ishizuka, 12α-Hydroxylated bile acid enhances accumulation of adiponectin and immunoglobulin A in the rat ileum, Scientific Reports, 10.1038/s41598-021-92302-z, 2021.11. |
| 5. |
Ai Takeyama, Asami Teramoto, Tianyu Wang, Takuya Hayashi, Yasutake Tanaka, Masao Sato, Bungo Shirouchi, Dietary lysophospholipids reduce lymphatic cholesterol transport compared with dietary phospholipids in thoracic lymph-duct cannulated rats, Lipids, 56, 6, 579-590, 2022.06. |
| 6. |
Zhe Jiang, Yuki Kimura, Bungo Shirouchi, Yasutake Tanaka, Wei-Ting Tsai, Xingyu Yuan, Masao Sato, Dietary egg white protein hydrolysate improves orotic acid-induced fatty liver in rats by promoting hepatic phospholipid synthesis and microsomal triglyceride transfer protein expression, The Journal of Nutritional Biochemistry, 10.1016/j.jnutbio.2021.108820., 2021.12. |
| 7. |
Motofumi Kumazoe, Yasutake Tanaka, Ren Yoshitomi, Yuki Marugame, Kwan-Woo Lee, Hiroaki Onda, Yoshinori Fujimura, Madoka Yonekura, Yasuyo Shimamoto, Hirofumi Tachibana, Glucosyl-hesperidin enhances the cyclic guanosine monophosphate-inducing effect of a green tea polyphenol EGCG., Journal of natural medicines, 10.1007/s11418-021-01538-6, 2021.06. |
| 8. |
＃Xingyu Yuan, Yutaro Minobe, Yasutake Tanaka, Yumi Fukuda, Yumiko Furukawa, Motonori Miyago, Takuya Mizokami, Wei-Ting Tsai, Zhe Jiang, Li-Tao Tong, Taiki Akasaka, Bungo Shirouchi, Yoshiko Toyosawa, Toshihiro Kumamaru, Masao Sato, α-Globulin-rich rice cultivar, low glutelin content-1 (LGC-1), decreases serum cholesterol concentration in exogenously hypercholesterolemic rats., Journal of the science of food and agriculture, 10.1002/jsfa.11312, 2021.05. |
| 9. |
Wei-Ting Tsai, Yuki Nakamura, Taiki Akasaka, Yoshinori Katakura, Yasutake Tanaka, Bungo Shirouchi, Zhe Jiang, Xingyu Yuan, Masao Sato, Soyasaponin ameliorates obesity and reduces hepatic triacylglycerol accumulation by suppressing lipogenesis in high-fat diet-fed mice, JOURNAL OF FOOD SCIENCE, 10.1111/1750-3841.15696, 86, 5, 2103-2117, 2021.04, Abstract: Soyasaponins are triterpenoid glycosides found in soybean. We investigated whether soyasaponin ameliorates lipid metabolism and its possible mechanisms. In C57BL/6J mice fed a high-fat diet (HFD), soyasaponin (SAP) was orally administered for 9 weeks. Additionally, we evaluated the effect of soyasapogenols on 3T3-L1 adipocytes. In HFD-fed mice, the SAP significantly reduced body weight by 7% and relative adipose tissue weight by 35%. X-ray computed tomography demonstrated that the SAP reduced visceral and subcutaneous adipose tissue weights during week 3 of feeding. The SAP reduced sterol regulatory element-binding protein-1c (SREBP-1c) mRNA levels by 32% in the epididymal adipose tissue, significantly decreasing the triacylglycerol (TAG) content by 37% and SREBP-1c and fatty acid synthase mRNA levels by 52% and 61%, respectively, in the liver. In 3T3-L1 adipocytes, soyasapogenol B significantly decreased lipid droplets. The SAP containing soyasaponin A and B as conjugates demonstrate anti-obesity effects by suppressing adipocyte differentiation and lipogenesis, with a preventive effect on hepatic TAG accumulation by suppressing lipogenesis. Practical Application: Soyasaponin is one of the oleanane triterpenoids in soybeans. We have demonstrated that soyasaponin potently reduces body weight and white adipose tissue weight, and hepatic triacylglycerol accumulation in high-fat diet-fed mice. Thus, soyasaponin is a beneficial compound to prevent obesity and fatty liver.. |
| 10. |
Ja-Young Lee, Hidehisa Shimizu, Masahito Hagio, Satoru Fukiya, Masamichi Watanabe, Yasutake Tanaka, Ga-Hyun Joe, Hitoshi Iwaya, Reika Yoshitsugu, Keidai Kikuchi, Misaki Tsuji, Nanako Baba, Takuma Nose, Koji Tada, Taketo Hanai, Shota Hori, Akari Takeuchi, Yumiko Furukawa, Bungo Shirouchi, Masao Sato, Tadasuke Ooka, Yoshitoshi Ogura, Tetsuya Hayashi, Atsushi Yokota, Satoshi Ishizuka, 12α-Hydroxylated bile acid induces hepatic steatosis with dysbiosis in rats, Biochim Biophys Acta Mol Cell Biol Lipids., 10.1016/j.bbalip.2020.158811., 1865, 12, 1865, 2020.10, There is an increasing need to explore the mechanism of the progression of non-alcoholic fatty liver disease. Steroid metabolism is closely linked to hepatic steatosis and steroids are excreted as bile acids (BAs). Here, we demonstrated that feeding WKAH/HkmSlc inbred rats a diet supplemented with cholic acid (CA) at 0.5 g/kg for 13 weeks induced simple steatosis without obesity. Liver triglyceride and cholesterol levels were increased accompanied by mild elevation of aminotransferase activities. There were no signs of inflammation, insulin resistance, oxidative stress, or fibrosis. CA supplementation increased levels of CA and taurocholic acid (TCA) in enterohepatic circulation and deoxycholic acid (DCA) levels in cecum with an increased ratio of 12α-hydroxylated BAs to non-12α-hydroxylated BAs. Analyses of hepatic gene expression revealed no apparent feedback control of BA and cholesterol biosynthesis. CA feeding induced dysbiosis in cecal microbiota with enrichment of DCA producers, which underlines the increased cecal DCA levels. The mechanism of steatosis was increased expression of Srebp1 (positive regulator of liver lipogenesis) through activation of the liver X receptor by increased oxysterols in the CA-fed rats, especially 4β-hydroxycholesterol (4βOH) formed by upregulated expression of hepatic Cyp3a2, responsible for 4βOH formation. Multiple regression analyses identified portal TCA and cecal DCA as positive predictors for liver 4βOH levels. The possible mechanisms linking these predictors and upregulated expression of Cyp3a2 are discussed. Overall, our observations highlight the role of 12α-hydroxylated BAs in triggering liver lipogenesis and allow us to explore the mechanisms of hepatic steatosis onset, focusing on cholesterol and BA metabolism.. |
| 11. |
Tomoko Shimoda, Shota Hori, Kenta Maegawa, Akari Takeuchi, Yeonmi Lee, Ga-Hyun Joe, Yasutake Tanaka, Hidehisa Shimizu, Satoshi Ishizuka., A low coefficient of variation in hepatic triglyceride concentration in an inbred rat strain, Lipids in Health and Disease, 10.1186/s12944-020-01320, 19, 1, 137, 2020.06. |
| 12. |
Yasutake Tanaka, Masahiro Ono, Motonori Miyago, Takahisa Suzuki, Yurika Miyazaki, Michio Kawano, Makoto Asahina, Bungo Shirouchi, Katsumi Imaizumi, Masao Sato, Low utilization of glucose in the liver causes diet-induced hypercholesterolemia in exogenously hypercholesterolemic rats, PloS one, 10.1371/journal.pone.0229669, 15, 3, 2020.01, Exogenously hypercholesterolemic (ExHC) rats develop diet-induced hypercholesterolemia (DIHC) when fed with dietary cholesterol. Previously, we reported that, under the high-sucrose-diet-feeding condition, a loss-of-function mutation in Smek2 results in low activity of fatty acid synthase (FAS) followed by the shortage of hepatic triacylglycerol content in ExHC rats and the onset of DIHC. However, the relationship between the Smek2 mutation and FAS dysfunction is still unclear. Here, we focused on carbohydrate metabolism, which provides substrates for FAS, and analyzed carbohydrate and lipid metabolisms in ExHC rats to clarify how the deficit of Smek2 causes DIHC. Male ExHC and SD rats were fed high-sucrose or high-starch diets containing 1% cholesterol for 2 weeks. Serum cholesterol levels of the ExHC rats were higher, regardless of the dietary carbohydrate. Hepatic triacylglycerol levels were higher in only the SD rats fed the high-sucrose diet. Moreover, the ExHC rats exhibited a diabetes-like status and accumulation of hepatic glycogen and low hepatic mRNA levels of liver-type phosphofructokinase (Pfkl), which encodes a rate-limiting enzyme for glycolysis. These results suggest that the glucose utilization, particularly glycolysis, is impaired in the liver of ExHC rats. To evaluate how the diet with extremely low glucose affect to DIHC, ExHC.BN-Dihc2BN, a congenic strain that does not develop DIHC, and ExHC rats were fed a high-fructose diet containing 1% cholesterol for 2 weeks. The serum cholesterol and hepatic triacylglycerol levels were similar in the strains. Results of water-soluble metabolite analysis with primary hepatocytes, an increase in fructose-6-phosphate and decreases in succinate, malate and aspartate in ExHC rats, support impaired glycolysis in the ExHC rats. Thus, the Smek2 mutation causes abnormal hepatic glucose utilization via downregulation of Pfkl expression. This abnormal glucose metabolism disrupts hepatic fatty acid synthesis and causes DIHC in the ExHC rats.. |
| 13. |
Dong Geun Lee, Shota Hori, Ohji Kohmoto, Shinri Kitta, Ryo Yoshida, Yasutake Tanaka, Hidehisa Shimizu, Keisuke Takahashi, Taizo Nagura, Hirokatsu Uchino, Satoru Fukiya, Atsushi Yokota, Satoshi Ishizuka, Ingestion of Difructose Anhydride III Partially Suppresses the Deconjugation and 7α-dehydroxylation of Bile Acids in Rats Fed With a Cholic Acid-Supplemented Diet, Biosci Biotechnol Biochem., 10.1080/09168451.2019.1597617., 83, 7, 1329-1335, 2019.03. |
| 14. |
Yasutake Tanaka, Kiyomi Takahashi, Jun Ichi Kato, Ai Sawazaki, Taiki Akasaka, Naoko Fujita, Toshihide Kumamaru, Yuhi Saito, Bungo Shirouchi, Masao Sato, Starch synthase IIIa and starch branching enzyme IIb-deficient mutant rice line ameliorates pancreatic insulin secretion in rats Screening and evaluating mutant rice lines with antidiabetic functionalities, British Journal of Nutrition, 10.1017/S0007114518000314, 119, 9, 970-980, 2018.01, Diabetes mellitus is a metabolic disease spreading worldwide that has been reported to worsen the development and progression of other diseases (cancer, vascular diseases and dementia). To establish functional rice lines with anti-postprandial hyperglycaemic effects, we developed mutant rice lines, which lack one or two gene(s) related to starch synthesis, and evaluated their effects. Powder of mutant rice lines or other grains was loaded to rats fasted overnight (oral grain powder loading test). Incremental area under time-concentration curves (iAUC) were calculated with monitored blood glucose levels. Rice lines with anti-postprandial hyperglycaemic effects were separated by cluster analysis with calculated iAUC. A double mutant rice #4019 (starch synthase IIIa (ss3a)/branching enzyme IIb (be2b)), one of the screened mutant rice lines, was fed to Goto-Kakizaki (GK) rats, an animal model for type 2 diabetes, for 5 weeks. Plasma levels of C-peptide, a marker of pancreatic insulin secretion, were measured with ELISA. For in vitro study, a rat pancreatic cell line was cultured with a medium containing rat serum which was sampled from rats fed #4019 diet for 2 d. After 24-h of incubation, an insulin secretion test was performed. Through the oral rice powder loading test, seven rice lines were identified as antidiabetic rice lines. The intake of #4019 diet increased plasma C-peptide levels of GK rats. This result was also observed in vitro. In rat serum added to cell medium, ornithine was significantly increased by the intake of #4019. In conclusion, the mutant rice #4019 promoted pancreatic insulin secretion via elevation of serum ornithine levels.. |
| 15. |
Michio Shimabukuro, Chinami Okawa, Hirotsugu Yamada, Shuhei Yanagi, Etsuko Uematsu, Noriko Sugasawa, Hirotsugu Kurobe, Yoichiro Hirata, Joo ri Kim-Kaneyama, Xiao Feng Lei, Shoichiro Takao, Yasutake Tanaka, Daiju Fukuda, Shusuke Yagi, Takeshi Soeki, Tetsuya Kitagawa, Hiroaki Masuzaki, Masao Sato, Masataka Sata, The pathophysiological role of oxidized cholesterols in epicardial fat accumulation and cardiac dysfunction a study in swine fed a high caloric diet with an inhibitor of intestinal cholesterol absorption, ezetimibe, Journal of Nutritional Biochemistry, 10.1016/j.jnutbio.2016.05.010, 35, 66-73, 2016.09, Oxidized cholesterols (oxycholesterols) in food have been recognized as strong atherogenic components, but their tissue distributions and roles in cardiovascular diseases remain unclear. To investigate whether accumulation of oxycholesterols is linked to cardiac morphology and function, and whether reduction of oxycholesterols can improve cardiac performance, domestic male swine were randomized to a control diet (C), high caloric diet (HCD) or HCD + Ezetimibe, an inhibitor of intestinal cholesterol absorption, group (HCD + E) and evaluated for: (1) distribution of oxycholesterol components in serum and tissues, (2) levels of oxycholesterol-related enzymes, (3) paracardial and epicardial coronary fat thickness, and (4) cardiac performance. Ezetimibe treatment for 8 weeks attenuated increases in oxycholesterols in the HCD group almost completely in liver, but reduced only levels of 4β-hydroxycholesterol in left ventricular (LV) myocardium. Ezetimibe treatment altered the expression of genes for cholesterol and fatty acid metabolism and decreased the expression of CYP3A46, which catabolizes cholesterol to 4β-hydroxycholesterol, strongly in liver. An increase in epicardial fat thickness and impaired cardiac performance in the HCD group were improved by ezetimibe treatment, and the improvement was closely related to the reduction in levels of 4β-hydroxycholesterol in LV myocardium. In conclusion, an increase in oxycholesterols in the HCD group was closely related to cardiac hypertrophy and dysfunction, as well as an increase in epicardial fat thickness. Ezetimibe may directly reduce oxycholesterol in liver and LV myocardium, and improve cardiac morphology and function.. |
| 16. |
Kazuo Erami, Yasutake Tanaka, Sayaka Kawamura, Motonori Miyago, Ai Sawazaki, Katsumi Imaizumi, Masao Sato, Dietary egg yolk supplementation improves low-protein-diet-induced fatty liver in rats, Journal of Nutritional Science and Vitaminology, 10.3177/jnsv.62.240, 62, 4, 240-248, 2016.01, Egg yolk is an important source of nutrients and contains different bioactive substances. In the present study, we studied the benefits of egg yolk in preventing low-protein- diet-induced fatty liver in rats. Rats were fed the following diets, which were based on the AIN-76 formula, for 2 wk: an adequate-protein diet containing 20% casein (C), a lowprotein diet containing 5% casein (LP-C), a low-protein diet supplemented with 12.5% egg yolk (LP-EY), and a low-protein diet supplemented with 4.1% egg yolk oil (LP-EYO). The lowprotein diets were adjusted to contain 4.13% protein and 4.7% lipids. The LP-C diet resulted in a greater increase in the liver trigriceride (TG) and the vacuolation and a greater decrease in the serum TG and free fatty acid (FFA) than did the C diet. These deviations in the serum and liver TG, serum FFA levels and the liver histopathology were corrected in rats fed the LP-EY diet but not in those fed the LP-EYO diet. Compared to rats fed the LP-C diet, although the activities of lipogenesis-related enzymes (fatty acid synthase, glucose-6-phosphate dehydrogenase, and malic enzyme) decreased in rats fed both of the LP-EY and LP-EYO diets, the level of the microsomal TG transfer protein (MTP) increased only in rats fed the LP-EY diet. Collectively, these results suggest that dietary egg yolk supplementation decreases the LP diet-induced accumulation of TG in the liver by increasing transport of TG in the liver, and egg yolk oil alone is not sufficient enough to bring about these benefits.. |
| 17. |
Yasutake Tanaka, Koji Nagao, Hideaki Nakagiri, Toshirou Nagaso, Yasue Iwasa, Haruhiko Mori, Makoto Asahina, Katsumi Imaizumi, Masao Sato, Unavailability of liver triacylglycerol increases serum cholesterol concentration induced by dietary cholesterol in exogenously hypercholesterolemic (ExHC) rats, Lipids in Health and Disease, 10.1186/1476-511X-13-19, 13, 1, 2014.01, Background: Exogenously hypercholesterolemic (ExHC) rats develop hypercholesterolemia and low hepatic triacylglycerol (TAG) levels when dietary cholesterol is loaded. The responsible gene Smek2 was identified via linkage analysis using the original strain Sprague-Dawley (SD) rats. In this study, we compared SD and ExHC rats to investigate a relationship between hypercholesterolemia and the low hepatic TAG levels observed in ExHC rats. Methods. Male 4-weeks-old ExHC and SD rats were fed a 1% cholesterol diet for 1 week. Serum and liver parameters were analyzed. Gene expression and enzyme activities related to TAG metabolism were also assessed. Results: We reproducibly observed higher serum cholesterol and lower hepatic TAG levels in ExHC rats than in SD rats. Golgi apparatus in the livers of ExHC rats secreted β-very-low-density lipoprotein (β-VLDL) that had higher cholesterol ester (CE) and lower TAG content than those in the β-VLDL secreted by SD rats. Gene expression related to fatty acid and TAG synthesis in ExHC rats was lower than that in SD rats. Enzymatic activities for fatty acid synthesis were also relatively lower in ExHC rats. Moreover, the fatty acid composition of hepatic and serum CE in ExHC rats showed that these CEs were not modified after secretion from the liver despite the similar activities of serum lecithin-cholesterol acyltransferase (LCAT) in ExHC rats to those in SD rats. Conclusions: Low production of liver TAG and secretion of CE-rich, TAG-poor β-VLDL without modification by LCAT in the circulation contributed to hypercholesterolemia induced by dietary cholesterol in ExHC rats.. |
| 18. |
Masaki Kato, Yusuke Ito, Yasutake Tanaka, Masao Sato, Katsumi Imaizumi, Nao Inoue, Ikuo Ikeda, SHRSP/Izm and WKY/NCrlCrlj rats having a missense mutation in Abcg5 deposited plant sterols in the body, but did not change their biliary secretion and lymphatic absorption-comparison with Jcl:Wistar and WKY/Izm rats, Bioscience, Biotechnology and Biochemistry, 10.1271/bbb.110667, 76, 4, 660-664, 2012.04, We had previously found plant sterols deposited in the bodies of stroke-prone spontaneously hypertensive rats (SHRSP)/Sea and Wistar Kyoto (WKY)/NCrlCrlj rats that had a missense mutation in the Abcg5 cDNA sequence that coded for ATP-binding cassette transporter (ABC) G5. We used SHRSP/Izm, WKY/ NCrlCrlj, and WKY/Izm rats in the present study to determine the mechanisms for plant sterol deposition in the body. Jcl:Wistar rats were used as a control strain. A diet containing 0.5% plant sterols fed to the rats resulted in plant sterol deposition in the body of SHRSP/Izm, but not in WKY/Izm or Jcl:Wistar rats. Only a single non-synonymous nucleotide change, G1747T, resulting in a conservative cysteine substitution for glycine at amino acid 583 (Gly583Cys) in Abcg5 cDNA was identified in the SHRSP/Izm and WKY/ NCrlCrlj rats. However, this mutation was not found in the WKY/Izm or Jcl:Wistar rats. No significant difference in the biliary secretion or lymphatic absorption of plant sterols was apparent between the rat strains with or without the missense mutation in Abcg5 cDNA. Our observations suggest that plant sterol deposition in rat strains with the missense mutation in Abcg5 cDNA can occur, despite there being no significant change in the biliary secretion or lymphatic absorption of plant sterols.. |
| 19. |
Li Tao Tong, Yoshinori Katakura, Sayaka Kawamura, Sanae Baba, Yasutake Tanaka, Miyako Udono, Yoshie Kondo, Kumi Nakamura, Katsumi Imaizumi, Masao Sato, Effects of Kurozu concentrated liquid on adipocyte size in rats, Lipids in Health and Disease, 10.1186/1476-511X-9-134, 9, 2010.11, Background. Kurozu concentrated liquid (KCL) is used as a health-promoting supplement for the treatment of disorders such as cancer, hyperlipidemia, and hypertension in Japan. We investigated the possible anti-obesity effects of KCL in rats. Methods. Male Sprague Dawley rats were fed American Institute of Nutrition 76 formula diet and were orally administrated KCL or acetic acid at a dose of 100 mg/kg body weight or deionized water for 4 weeks. Adipocyte size, DNA content in subcutaneous adipose tissue, lipid levels in the serum and liver, and the rate of fatty acid excretion were determined. Effects of KCL on pancreatic lipase activity and 3T3-L1 preadipocyte differentiation were investigated in vitro. Results. In the KCL group, the average adipocyte size in subcutaneous and perirenal adipose tissues was significantly reduced. The KCL-administered rats displayed greater numbers of small adipocytes in the subcutaneous, perirenal and mesenteric adipose tissues than did rats from the other groups. In the KCL group, the DNA content in subcutaneous adipose tissue was significantly increased. The rate of fatty acid excretion was significantly increased in the KCL group. Furthermore, KCL significantly inhibited pancreatic lipase activity in vitro, and also significantly inhibited fat accumulation and mRNA expression of fatty acid binding protein 2 (aP2) and peroxisome proliferator-activated (PPAR) in 3T3-L1 preadipocyte. The levels of serum and liver lipids, the concentration of serum glucose, and the levels of adiponectin were similar among the 3 groups. Conclusion. Oral administration of KCL decreases the adipocyte size via inhibition of dietary fat absorption and reductions of PPAR and aP2 mRNA expression levels in adipocytes.. |
