2022/09/25 更新

写真a

スズキ ヒロシ
鈴木 浩史
SUZUKI Hiroshi
所属
研究推進機構 特任助教
職名
特任助教
外部リンク

学位

  • 学士(医学) ( 2007年3月   金沢医科大学 )

研究キーワード

  • 代謝

  • 糖尿病

  • 内分泌

  • 機能性食品

研究分野

  • ライフサイエンス / 代謝、内分泌学

  • ライフサイエンス / 食品科学  / 農芸化学

経歴(researchmap)

  • 新潟大学   研究推進機構   特任助教

    2016年7月 - 現在

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    国名:日本国

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  • 新潟大学   医歯学総合病院 内分泌・代謝内科

    2013年4月 - 2013年9月

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  • 立川綜合病院   内分泌内科

    2011年10月 - 2013年3月

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  • 新潟大学   医歯学総合病院 内分泌・代謝内科

    2010年4月 - 2011年9月

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  • 新潟市民病院   内分泌・代謝内科

    2009年4月 - 2010年3月

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    国名:日本国

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  • 済生会新潟第二病院   臨床研修医

    2007年4月 - 2009年3月

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    国名:日本国

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▶ 全件表示

経歴

  • 新潟大学   研究推進機構   特任助教

    2016年7月 - 現在

学歴

  • 新潟大学   大学院医歯学総合研究科   内分泌代謝内科

    2013年10月 - 2021年9月

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    国名: 日本国

    備考: 大学院 博士課程

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  • 金沢医科大学   医学部   医学科

    2001年4月 - 2007年3月

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    国名: 日本国

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論文

  • マウスにおける越後白雪茸の摂取による非アルコール性脂肪性肝炎の進行抑制効果

    鈴木 浩史, 渡辺 賢一, Arumugam Somasundaram, Yellurkar Manoj Limbraj, Sreedhar Remya, Afrin Rejina, 曽根 博仁

    機能性食品と薬理栄養   15 ( 3 )   184 - 184   2021年12月

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    記述言語:日本語   出版者・発行元:(株)インフォノーツパブリッシング  

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  • 副腎腫瘍とK低値で内分泌疾患を疑うもGitelman症候群と考えた1例

    中村 博至, 矢口 雄大, 佐藤 孝明, 山本 正彦, 石黒 創, 北澤 勝, 松林 泰弘, 石澤 正博, 鈴木 浩史, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    日本内分泌学会雑誌   97 ( 2 )   559 - 559   2021年10月

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    記述言語:日本語   出版者・発行元:(一社)日本内分泌学会  

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  • 【脂質異常症の動向と治療の展望-ここまで到達した高コレステロール血症の治療】機能性表示食品と脂質異常

    鈴木 浩史, 渡辺 賢一, 曽根 博仁

    カレントテラピー   39 ( 9 )   871 - 875   2021年9月

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    記述言語:日本語   出版者・発行元:(株)ライフメディコム  

    機能性表示食品は、科学的根拠に基づいた機能性を表示した食品とされ、必要な事項が事業者より消費者庁長官に届けられたものである。機能性表示食品は、特定保健用食品(トクホ)と異なり、消費者庁長官の個別の許可を受けたものではない。消費者庁のホームページで「中性脂肪」、「コレステロール」について機能性表示を行っている販売中の食品の機能性関与成分としては、リコピン、DHA・EPAが挙げられる。リコピンの脂質代謝改善作用については統一した見解がない。DHA・EPAについては、二次予防においてはエビデンスがあるが、一次予防についてはまだその有用性は証明されていない。その他にも脂質代謝改善作用が期待できる食品はあるが、いずれも実際に臨床現場で使用できるエビデンスが確立されているとは言い難い。今後、さまざまな食品によるヒト臨床試験が進んでいき、一次予防が可能な食品が現れることを期待したい。(著者抄録)

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  • 粘液水腫性昏睡に急性膵炎を合併した一例

    齋藤 啓輔, 矢口 雄大, 滝澤 祥子, 西井 郁生, 竹内 亮, 山本 正彦, 川田 亮, 石黒 創, 北澤 勝, 松林 泰弘, 鈴木 浩史, 岩永 みどり, 山田 貴穂, 藤原 和哉, 曽根 博仁

    日本内分泌学会雑誌   97 ( Suppl.Update )   38 - 40   2021年7月

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    記述言語:日本語   出版者・発行元:(一社)日本内分泌学会  

    72歳男性。入院6日前より近医にて低Na血症、甲状腺機能低下に対しレボチロキシン内服を開始されたが効果はなく、意識障害となって救急搬送された。20歳代よりBasedow病の既往がある。入院時現症、血液検査、画像検査各所見より、急性膵炎疑い、粘液水腫性昏睡の診断基準で確実例となり粘液水腫昏睡と診断した。ヒドロコルチゾン、レボチロキシン投与、ドパミン塩酸塩の持続静注、3%生理食塩水を開始し、低体温に対するウォームアップ、急性膵炎疑いに対する細胞外液大量投与とウリナスタチン投与を行った結果、全身状態は順調に改善した。経過中、腹痛や背部痛の訴えはなかった。甲状腺エコー所見より、粘液水腫性昏睡は甲状腺機能低下を伴う未治療橋本病により発症し、粘液水腫性昏睡による低体温、虚血障害に起因して急性膵炎を発症したと考えられた。

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01160&link_issn=&doc_id=20210811280012&doc_link_id=%2Fcq6naibu%2F2021%2F0097s1%2F013%2F0038-0040%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcq6naibu%2F2021%2F0097s1%2F013%2F0038-0040%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • Association of increased hepatic insulin clearance and change in serum triglycerides or β-hydroxybutyrate concentration via the sodium/glucose-cotransporter 2 inhibitor tofogliflozin. 国際誌

    Yasuhiro Matsubayashi, Akihiro Yoshida, Hideki Suganami, Taeko Osawa, Kazuo Furukawa, Hiroshi Suzuki, Kazuya Fujihara, Shiro Tanaka, Kohei Kaku, Hirohito Sone

    Diabetes, obesity & metabolism   22 ( 6 )   947 - 956   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIMS: Obesity and hepatic fat accumulation diminish hepatic insulin clearance, which can cause hyperinsulinaemia. Sodium/glucose-cotransporter 2 inhibitors (SGLT2-is) improve insulin resistance and hyperinsulinaemia by weight loss via increased urinary glucose excretion in type 2 diabetes. However, there are few reports of the influence of SGLT2-is on hepatic insulin clearance. We examined the impact of an SGLT2-i on hepatic insulin clearance and explored the clinical influence associated with changes in hepatic insulin clearance via an SGLT2-i and the mechanism of the effects of SGLT2-i. MATERIALS AND METHODS: Data were analysed from 419 patients with type 2 diabetes controlled by diet and exercise. Patients received a placebo or the SGLT2-i tofogliflozin (TOFO) (placebo: n = 56; TOFO: n = 363) orally once daily for ≥24 weeks. Hepatic insulin clearance was calculated from the ratio of areas under the curve (AUC) of C-peptide and insulin levels derived from oral meal tolerance test data (C-peptide AUC0-120 min /insulin AUC0-120 min : HICCIR ). The correlation of HICCIR via the SGLT2-i with other clinical variables was analysed using multivariate analysis. RESULTS: HICCIR was significantly increased via TOFO at week 24. Furthermore, with TOFO insulin and triglyceride (TG) levels were significantly reduced (P < 0.001) and β-hydroxybutyrate (BHB) was significantly elevated (P < 0.001). Changes in HICCIR were significantly correlated with changes in TG and BHB via TOFO. CONCLUSIONS: Increased HICCIR was significantly associated with reduced TG via TOFO and contributed to the greater increase in BHB compared with placebo in addition to the correction of hyperinsulinaemia.

    DOI: 10.1111/dom.13980

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  • Higher pulse pressure predicts initiation of dialysis in Japanese patients with diabetes. 国際誌

    Taeko Osawa, Kazuya Fujihara, Mayuko Harada, Masahiko Yamamoto, Masahiro Ishizawa, Hiroshi Suzuki, Hajime Ishiguro, Yasuhiro Matsubayashi, Hiroyasu Seida, Nauta Yamanaka, Shiro Tanaka, Hitoshi Shimano, Satoru Kodama, Hirohito Sone

    Diabetes/metabolism research and reviews   35 ( 3 )   e3120   2019年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIMS: To determine incidence and predictors of starting dialysis in patients with diabetes emphasizing blood pressure variables. METHODS: A nationwide database with claim data on 18 935 people (15 789 men and 3146 women) with diabetes mellitus aged 19 to 72 years in Japan was used to elucidate predictors for starting dialysis. Initiation of dialysis was determined from claims using ICD-10 codes and medical procedures. Using multivariate Cox modelling, interactions between glycaemic and blood pressure values were determined. RESULTS: During a median follow-up of 5.3 years, incidence of dialysis was 0.81 per 1000 person-years. Multivariate analysis of a model involving systolic and diastolic blood pressure (SBP and DBP) simultaneously as covariates showed that hazard ratios (HRs) for starting dialysis for each 1-SD elevation in SBP and DBP were 2.05 (95% confidence interval 1.58-2.64) and 0.66 (0.50-0.88), respectively, implying that pulse pressure (PP) was a promising predictor. For confirmation, a model involving SBP and PP simultaneously as covariates demonstrated that HRs for each 1-SD elevation in SBP and PP were 1.09 (0.81-1.48) and 1.54 (1.14-2.08), respectively, with PP the more potent predictor. Compared with HbA1c <8% and PP <60 mmHg, the HR for those with HbA1c ≥8% and PP ≥60 mmHg was 6.32 (3.42-11.7). CONCLUSIONS: In our historical cohort analysis, SBP and PP were independent predictors for starting dialysis. PP was the more potent, suggesting the contribution of increased arterial stiffness to the incidence of dialysis. Future studies are needed to conclude the independent influence of PP and HbA1c on dialysis considering other risk factors.

    DOI: 10.1002/dmrr.3120

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  • Comparative evaluation of torasemide and spironolactone on adverse cardiac remodeling in a rat model of dilated cardiomyopathy. 国際誌

    Somasundaram Arumugam, Remya Sreedhar, Vengadeshprabhu Karuppagounder, Meilei Harima, Masahiko Nakamura, Hiroshi Suzuki, Hirohito Sone, Kenichi Watanabe

    Cardiovascular therapeutics   35 ( 5 )   2017年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Chronic heart failure (CHF) involves fluid retention and volume overload, leading to impaired cardiac function. In these conditions, diuretic agents are most commonly used to treat edema and thereby reducing the volume load on the failing heart. There are several other beneficial effects of diuretics apart from their action on urinary excretion. METHODS: To identify the effects of diuretic agents on adverse cardiac remodeling in CHF, this study was carried out, where we have compared the effects of torasemide and spironolactone in a rat model of dilated cardiomyopathy induced by porcine cardiac myosin-mediated experimental autoimmune myocarditis. RESULTS: Cardiac protein expression levels of inflammation, endoplasmic reticulum stress, and fibrosis markers were upregulated in the hearts of CHF rats, while treatment with either torasemide or spironolactone has downregulated their expression. The effect produced by spironolactone on cardiac fibrosis markers was comparably lesser than torasemide. Further, immunohistochemical analysis and histopathological studies have provided evidence to confirm the beneficial effects of these drugs on adverse cardiac remodeling in rats with CHF. CONCLUSION: Torasemide treatment has benefits against adverse cardiac remodeling in CHF rats, which was better than the protection offered by spironolactone.

    DOI: 10.1111/1755-5922.12283

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  • Curcumin reduces the risk of chronic kidney damage in mice with nonalcoholic steatohepatitis by modulating endoplasmic reticulum stress and MAPK signaling. 国際誌

    Mst Rejina Afrin, Somasundaram Arumugam, Md Azizur Rahman, Vengadeshprabhu Karuppagounder, Meilei Harima, Hiroshi Suzuki, Shizuka Miyashita, Kenji Suzuki, Kazuyuki Ueno, Hiroyuki Yoneyama, Kenichi Watanabe

    International immunopharmacology   49   161 - 167   2017年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Developing confirmation recommends that in patients with dynamic type of NAFLD, particularly nonalcoholic steatohepatitis (NASH) may have the pathogenic parts in the advancement of kidney damage. In this study we have examined the impact of curcumin on NASH instigated chronic kidney damage (CKD) and the putative mechanisms. To prepare this NASH model, neonatal C57BL/6J male mice were exposed to low-dose streptozotocin (STZ) and were fed high-fat diet (HFD) at the age of 4weeks and continued up to 14weeks, curcumin was given at 100mg/kg dose by oral gavage daily after 10weeks of STZ injection and continued for 4weeks along with HFD feeding. NASH incited mice demonstrated nephrotoxicity as proved by declining renal capacity, which was evaluated by measuring blood urea nitrogen and creatinine in serum and histopathological variations from the norm. These progressions were switched by curcumin treatment, which brought about huge change in renal capacity. Furthermore, curcumin markedly decreased NAD(P)H oxidase subunits (p67phox, p47phox, p22phox), nitrotyrosine and CYP2E1 renal protein expression as well as reduced pro-inflammatory cytokine expression (TNFα, IL-1β, IFNγ). Renal protein expression of mitogen activated protein kinases (MAPKs) (p-JNK, p-ERK1/2) and glucose regulated protein 78, CHOP were increased in NASH induced mice and curcumin treatment attenuated these increased expressions. In addition, curcumin treatment also decreased the apoptosis signaling proteins (cleaved caspase-3, cleaved caspase-12) in the NASH kidney. Taken together, our results suggest that curcumin preserves the renal function, probably by attenuating the ER stress mediated MAPK signaling.

    DOI: 10.1016/j.intimp.2017.05.035

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  • Curcumin ameliorates liver damage and progression of NASH in NASH-HCC mouse model possibly by modulating HMGB1-NF-κB translocation. 国際誌

    Rejina Afrin, Somasundaram Arumugam, Azizur Rahman, Mir Imam Ibne Wahed, Vengadeshprabhu Karuppagounder, Meilei Harima, Hiroshi Suzuki, Shizuka Miyashita, Kenji Suzuki, Hiroyuki Yoneyama, Kazuyuki Ueno, Kenichi Watanabe

    International immunopharmacology   44   174 - 182   2017年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Curcumin, a phenolic compound, has a wide spectrum of therapeutic effects such as antitumor, anti-inflammatory, anti-cancer and so on. The study aimed to investigate the underlying mechanisms of curcumin to protect liver damage and progression of non-alcoholic steatohepatitis (NASH) in a novel NASH-hepatocellular carcinoma (HCC) mouse model. To induce this model neonatal C57BL/6J male mice were exposed to low-dose streptozotocin and were fed a high-fat diet (HFD) from the age of 4weeks to 14weeks. Curcumin was given at 100mg/kg dose daily by oral gavage started at the age of 10weeks and continued until 14weeks along with HFD feeding. We found that curcumin improved the histopathological changes of the NASH liver via reducing the level of steatosis, fibrosis associated with decreasing serum aminotransferases. In addition, curcumin treatment markedly reduced the hepatic protein expression of oxidative stress, pro-inflammatory cytokines, and chemokines including interferon (IFN) γ, interleukin-1β and IFNγ-inducible protein 10, in NASH mice. Furthermore, curcumin treatment significantly reduced the cytoplasmic translocation of high mobility group box 1 (HMGB1) and the protein expression of toll like receptor 4. Nuclear translocation of nuclear factor kappa B (NF-κB) was also dramatically attenuated by the curcumin in NASH liver. Curcumin treatment effectively reduced the progression of NASH to HCC by suppressing the protein expression of glypican-3, vascular endothelial growth factor, and prothrombin in the NASH liver. Our data suggest that curcumin reduces the progression of NASH and liver damage, which may act via inhibiting HMGB1-NF-κB translocation.

    DOI: 10.1016/j.intimp.2017.01.016

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  • Comparative effects of torasemide and furosemide on gap junction proteins and cardiac fibrosis in a rat model of dilated cardiomyopathy. 国際誌

    Kenichi Watanabe, Remya Sreedhar, Rajarajan A Thandavarayan, Vengadeshprabhu Karuppagounder, Vijayasree V Giridharan, Shanish Antony, Meilei Harima, Masahiko Nakamura, Kenji Suzuki, Hiroshi Suzuki, Hirohito Sone, Somasundaram Arumugam

    BioFactors (Oxford, England)   43 ( 2 )   187 - 194   2017年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Cardiac fibrosis is the major hallmark of adverse cardiac remodeling in chronic heart failure (CHF) and its therapeutic targeting might help against cardiac dysfunction during chronic conditions. Diuretic agents are potentially useful in these cases, but their effects on the cardiac fibrosis pathogenesis are yet to be identified. This study was designed to identify and compare the effects of diuretic drugs torasemide and furosemide on cardiac fibrosis in a rat model of dilated cardiomyopathy induced by porcine cardiac myosin mediated experimental autoimmune myocarditis. Gap junction proteins, connexin-43 and N-cadherin, expressions were downregulated in the hearts of CHF rats, while torasemide treatment has upregulated their expression. Western blotting and immunohistochemical analysis for various cardiac fibrosis related proteins as well as histopathological studies have shown that both drugs have potential anti-fibrotic effects. Among them, torasemide has superior efficacy in offering protection against adverse cardiac remodeling in the selected rat model of dilated cardiomyopathy. In conclusion, torasemide treatment has potential anti-fibrotic effect in the hearts of CHF rats, possibly via improving the gap junction proteins expression and thereby improving the cell-cell interaction in the heart. © 2016 BioFactors, 43(2):187-194, 2017.

    DOI: 10.1002/biof.1332

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  • Le Carbone, a charcoal supplement, modulates DSS-induced acute colitis in mice through activation of AMPKα and downregulation of STAT3 and caspase 3 dependent apoptotic pathways. 国際誌

    Mst Rejina Afrin, Somasundaram Arumugam, Md Azizur Rahman, Vengadeshprabhu Karuppagounder, Remya Sreedhar, Meilei Harima, Hiroshi Suzuki, Takashi Nakamura, Shizuka Miyashita, Kenji Suzuki, Kazuyuki Ueno, Kenichi Watanabe

    International immunopharmacology   43   70 - 78   2017年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Le Carbone (LC) is a charcoal supplement, which contains a large amount of dietary fibers. Several studies suggested that charcoal supplement may be beneficial for stomach disorders, diarrhea, gas and indigestion. But no studies address whether LC intake would suppress inflammation, cell proliferation or disease progression in colitis. In the present study, the effect of LC on experimental colitis induced by dextran sulfate sodium (DSS) in mice and its possible mechanism of action were examined. A study was designed for 8days, using C57BL/6 female mice that were administered with 3% DSS in drinking water for 7days followed by another 1day consumption of normal water with or without treatment. LC suspension was administered daily for 7days via oral gavage using 5mg/mouse in treatment group and normal group was supplied with drinking water. LC suspension significantly attenuated the loss of body weight and shortening of colon length induced by DSS. The disease activity index, histopathologic changes were significantly reduced by LC treatment. The inflammatory mediators TNFα, IL-1β, p-STAT3 and p-NF-κB induced in the colon by DSS were markedly suppressed by LC. The increased activation of AMPKα in the colon was also detected in LC group. Furthermore, the apoptotic marker protein cleaved caspase 3 was down-regulated and anti-apoptotic proteins Bcl2 and Bcl-xL were significantly up-regulated by LC treatment. Taken together, our results demonstrate the ability of LC to inhibit inflammation, apoptosis and give some evidence for its potential use as adjuvant treatment of inflammatory bowel disease.

    DOI: 10.1016/j.intimp.2016.10.023

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  • Erratum to "Hypothalamic glucagon signaling in fasting hypoglycemia" [Life Sci. 153 (2016) 118-123]. 国際誌

    Vigneshwaran Pitchaimani, Somasundaram Arumugam, Rajarajan Amirthalingam Thandavarayan, Vengadeshprabhu Karuppagounder, Mst Rejina Afrin, Remya Sreedhar, Meilei Harima, Hiroshi Suzuki, Shizuka Miyashita, Kenji Suzuki, Masahiko Nakamura, Kazuyuki Ueno, Kenichi Watanabe

    Life sciences   160   1 - 1   2016年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.lfs.2016.07.003

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  • Fasting time duration modulates the onset of insulin-induced hypoglycemic seizures in mice. 国際誌

    Vigneshwaran Pitchaimani, Somasundaram Arumugam, Rajarajan Amirthalingam Thandavarayan, Vengadeshprabhu Karuppagounder, Mst Rejina Afrin, Remya Sreedhar, Meilei Harima, Hiroshi Suzuki, Shizuka Miyashita, Takashi Nakamura, Kenji Suzuki, Masahiko Nakamura, Kazuyuki Ueno, Kenichi Watanabe

    Epilepsy research   125   47 - 51   2016年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: Fasting (48h) in mice causes resistance to insulin-induced hypoglycemic seizures (IIHS) but in rats fasting (14-16h) predisposes IIHS. So we suspect the duration of fasting may possibly affect the onset of seizures and in this study, we investigated the IIHS by administering 8 Units (U) insulin (INS)/k.g., intraperitoneally to 8 weeks old male C57BL6/J mice. METHODS: The mice were divided into group 1 (non-fasted), group 2 (6h fasted) and group 3 (24h fasted) and we administered the 8U INS. The first behavioral hypoglycemic seizure symptoms such as jump, clonus or barrel rotations considered as seizure onset and we analyzed the blood glucose level (BGL) and serum beta-hydroxybutyrate (BHB) level. RESULTS: The time of first seizure onset in group 1 was 109.7±4.3min, group 2 was 46.50±3.9min and group 3 was 165.4±13.26min. The seizure onset time in group 2 was significantly decreased compared to group 1. The seizure onset time in group 3 was significantly increased compared to group 1 and group 2. The decreased BGL after INS administration was correlated with the seizure onset time in group 1 and group 2 but not in group 3. The BHB level in group 3 was significantly higher compared to group 1 and 2. CONCLUSION: Our data show that the fasting time duration significantly modulates the onset of hypoglycemic seizures. The opposite effect of 6h or 24h fasting time duration is likely caused by different BHB levels.

    DOI: 10.1016/j.eplepsyres.2016.06.009

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  • Curcumin Ameliorates Progression of Liver Tumors and Damage through Inhibition of Oxidative Stress, Inflammation, and Fibrosis in Nonalcoholic Steatohepatitis-Hepatocellular Carcinoma Mouse Model

    M. S. T. Rejina Afrin, Somasundaram Arumugam, M. D. Azizur Rahman, Vigneshwaran Pitchaimani, Vengadeshprabhu Karuppagounder, Remya Sreedhar, Meilei Harima, Hiroshi Suzuki, Shizuka Miyashita, Kenji Suzuki, Hiroyuki Yoneyama, Kazuyuki Ueno, Kenichi Watanabe

    DIABETES   65   A579 - A579   2016年6月

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    記述言語:英語   出版者・発行元:AMER DIABETES ASSOC  

    Web of Science

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  • Hypothalamic glucagon signaling in fasting hypoglycemia. 国際誌

    Vigneshwaran Pitchaimani, Somasundaram Arumugam, Rajarajan Amirthalingam Thandavarayan, Vengadeshprabhu Karuppagounder, Mst Rejina Afrin, Remya Sreedhar, Meilei Harima, Hiroshi Suzuki, Shizuka Miyashita, Kenji Suzuki, Masahiko Nakamura, Kazuyuki Ueno, Kenichi Watanabe

    Life sciences   153   118 - 23   2016年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIMS: Sustained glucagon infusion increases hepatic glucose production, but this effect is transient due to hypothalamic glucagon signaling. In hypoglycemia, glucagon acts as a major defense to sustain the blood glucose level and this raises the question regarding glucagon signaling associated glucose production in prolonged fasting hypoglycemia. In this study, we investigated the proteins associated with hypothalamic glucagon signaling and liver gluconeogenesis during fasting hypoglycemia. MAIN METHODS: 8-9week old, male C57BL6/J mice were fasted for 4, 8, 12, 18, 24, 30, 36 or 42h. In the hypothalamus, we investigated glucagon signaling by analyzing the glucagon receptor and its downstream protein, peroxisome proliferator-activated receptor-gamma coactivator 1 (PGC-1) expression. In the liver, we investigated gluconeogenesis by analyzing p-protein kinase A (PKA)(Ser/Thr) substrate and phosphoenolpyruvate carboxykinase - cytosolic (PEPCK-C) expression using the western blotting technique. KEY FINDINGS: The elevated or trended higher hypothalamic glucagon receptor and PGC-1 expressions at 18 and 42h were correlated with the attenuated liver p-PKA(Ser/Thr) substrate expression. The attenuated hypothalamic glucagon receptor and PGC-1 expressions at 12, 24, 30 and 36h were correlated with the elevated or trended higher liver p-PKA(Ser/Thr) substrate expression. SIGNIFICANCE: The hypothalamic glucagon signaling during fasting hypoglycemia might have been modulated by circadian rhythm and this possibly attenuates the liver p-PKA(Ser/Thr) substrate to modify the gluconeogenesis pathway. This mechanism will help to understand the hyperglucagonemia associated complications in diabetes.

    DOI: 10.1016/j.lfs.2016.04.006

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  • Soluble LR11 is a novel biomarker for vascular lesions late after Kawasaki disease. 国際誌

    Kenichi Watanabe, Hiroshi Suzuki, Meizi Jiang, Hisanori Haniu, Fujito Numano, Satoshi Hoshina, Akihiko Saitoh, Makoto Uchiyama, Hideaki Bujo

    Atherosclerosis   246   94 - 7   2016年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: Coronary artery lesions (CALs) and a risk for early onset of atherosclerosis are major concerns following Kawasaki disease (KD). Intimal smooth muscle cells (SMCs) have an important role in vascular lesions in KD. It is known that soluble LR11 (sLR11) is a novel biomarker for vascular lesions and LR11 is markedly expressed in intimal SMCs in atherosclerotic lesions. In this study, we hypothesized that sLR11 reflects the presence of vascular lesions late after KD. METHODS: Twenty-three age-matched controls (group 1) and 59 patients with a history of KD were enrolled; 36 with KD had normal coronary arteries or regressed aneurysms (group 2), and 23 had CALs (group 3). RESULTS: Serum sLR11 levels in group 3 (median, interquartile range (IQR): 11.1 ng/mL, 9.3-13.9 ng/mL) were significantly higher than those in groups 1 (8.4 ng/mL, 7.1-10.2 ng/mL, p < 0.001) and 2 (9.0 ng/mL, 7.7-10.1 ng/mL, p < 0.01). Levels of sLR11 were positively correlated with levels of high-sensitivity C-reactive protein (r = 0.480, p < 0.01) and lipoprotein (a) (r = 0.486, p < 0.01). CONCLUSION: These findings suggest that sLR11 reflects the development of vascular lesions in patients with serious CALs.

    DOI: 10.1016/j.atherosclerosis.2015.12.035

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  • Attenuation of Endoplasmic Reticulum Stress-Mediated Liver Damage by Mulberry Leaf Diet in Streptozotocin-Induced Diabetic Rats. 国際誌

    Rejina Afrin, Somasundaram Arumugam, Mir Imam Ibne Wahed, Vigneshwaran Pitchaimani, Vengadeshprabhu Karuppagounder, Remya Sreedhar, Meilei Harima, Hiroshi Suzuki, Shizuka Miyashita, Takashi Nakamura, Kenji Suzuki, Masahiko Nakamura, Kazuyuki Ueno, Kenichi Watanabe

    The American journal of Chinese medicine   44 ( 1 )   87 - 101   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Endoplasmic reticulum stress (ERS) plays a crucial role in the development of insulin resistance and diabetes mellitus. Although antidiabetic use of mulberry leaves (MLs) has been popular due to their many anti-oxidative flavonoid compounds and free radical scavenging effects, ML's effects on ERS in experimental diabetic hepatocyte injury remain unknown. To investigate how ML affect ERS in diabetic liver, Sprague-Dawley (SD) rats were assigned to induce diabetes by a single intraperitoneal injection of streptozocin (STZ; 55 mg/kg) and fed with either normal chow or a diet containing 25% mulberry leaf powder diet (MLD) and examined for 56 days. We observed that MLD improved the rats' morphological and histopathological changes. Levels of ERS markers such as phosphorylated double-stranded RNA-dependent protein kinase-like endoplasmic reticulum kinase (PERK) and X-box binding protein 1 (XBP1) and the protein expression of glucose regulated protein 78 (GRP78) were significantly higher in the diabetic liver compared to normal liver. MLD for 8 weeks significantly reduced all of these markers. MLD also significantly decreased hepatocyte apoptosis, hepatic macrophage recruitment, cellular infiltration, and CCAAT/enhancer-binding protein homologous protein (CHOP), tumor necrosis factor receptor associated factor 2 (TRAF2), interleukin 1[Formula: see text] (IL-1[Formula: see text]) and sterol regulatory element binding protein isoform 1c (SREBP 1c) levels in diabetic liver. These results may suggest that MLs can preserve hepatic function in experimental diabetes by modulating ERS mediated apoptosis and liver damage.

    DOI: 10.1142/S0192415X16500063

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  • Tannic acid modulates NFκB signaling pathway and skin inflammation in NC/Nga mice through PPARγ expression. 国際誌

    Vengadeshprabhu Karuppagounder, Somasundaram Arumugam, Rajarajan Amirthalingam Thandavarayan, Vigneshwaran Pitchaimani, Remya Sreedhar, Rejina Afrin, Meilei Harima, Hiroshi Suzuki, Mayumi Nomoto, Shizuka Miyashita, Kenji Suzuki, Masahiko Nakamura, Kazuyuki Ueno, Kenichi Watanabe

    Cytokine   76 ( 2 )   206 - 213   2015年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Polyphenolic compound tannic acid, which is mainly found in grapes and green tea, is a potent antioxidant with anticarcinogenic activities. In this present study, we hypothesized that tannic acid could inhibit nuclear factor (NF)κB signaling and inflammation in atopic dermatitis (AD) NC/Nga mice. We have analyzed the effects of tannic acid on dermatitis severity, histopathology and expression of inflammatory signaling proteins in house dust mite extract induced AD mouse skin. In addition, serum levels of T helper (Th) cytokines (interferon (IFN)γ, interleukin (IL)-4) were measured by enzyme-linked immunosorbent assay. Treatment with tannic acid ameliorated the development of AD-like clinical symptoms and effectively inhibited hyperkeratosis, parakeratosis, acanthosis, mast cells and infiltration of inflammatory cells in the AD mouse skin. Serum levels of IFNγ and IL-4 were significantly down-regulated by tannic acid. Furthermore, tannic acid treatment inhibited DfE induced tumor necrosis factor (TNF)α, high mobility group protein (HMG)B1, receptor for advanced glycation end products (RAGE), extracellular signal-regulated kinase (ERK)1/2, NFκB, cyclooxygenase (COX)2, IL-1β and increased the protein expression of peroxisome proliferator-activated receptor (PPAR)γ. Taken together, our results demonstrate that, DfE induced skin inflammation might be mediated through NFκB signaling and tannic acid may be a potential therapeutic agent for AD, which may possibly act via induction of PPARγ protein.

    DOI: 10.1016/j.cyto.2015.05.016

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  • Naringenin ameliorates daunorubicin induced nephrotoxicity by mitigating AT1R, ERK1/2-NFκB p65 mediated inflammation. 国際誌

    Vengadeshprabhu Karuppagounder, Somasundaram Arumugam, Rajarajan Amirthalingam Thandavarayan, Vigneshwaran Pitchaimani, Remya Sreedhar, Rejina Afrin, Meilei Harima, Hiroshi Suzuki, Kenji Suzuki, Masahiko Nakamura, Kazuyuki Ueno, Kenichi Watanabe

    International immunopharmacology   28 ( 1 )   154 - 9   2015年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Inflammation and oxidative stress play important roles in the progression of renal damage. The natural polyphenol naringenin is known to exert potent antioxidant and anti-inflammatory effects. In this study, we have investigated the effect of naringenin on kidney dysfunction, fibrosis, endoplasmic reticulum (ER) stress, angiotensin II type I receptor (AT1R) expression and inflammation in daunorubicin (DNR) induced nephrotoxicity model. Nephrotoxicity was induced in rats by intravenous injection of DNR at a cumulative dose of 9 mg/kg. After 1 week, naringenin (20mg/kg/day. p.o) was administered daily for 6 weeks. Biochemical studies were performed to evaluate renal function. Western blotting was performed to measure the protein levels of AT1R, endothelin (ET)1, ET receptor type A (ETAR), extracellular signal-regulated kinase (ERK)1/2, nuclear factor (NF)κB p65, peroxisome proliferator activated receptor (PPAR)γ, oxidative/ER stress, apoptosis, and inflammatory markers in the kidney of DNR treated rats. Histopathological analysis was done using hemotoxylin eosin and Masson trichrome stained renal sections to investigate the structural abnormalities and fibrosis. DNR treated rats suffered from nephrotoxicity as evidenced by worsened renal function, increased blood urea nitrogen, serum creatinine levels in renal tissues and histopathogical abnormalities. Treatment with naringenin mitigated these changes. Furthermore, naringenin up regulated PPARγ and down regulated AT1R, ET1, ETAR, p-ERK1/2, p-NFκB p65, ER stress, apoptosis, and inflammatory markers. Our results suggest that naringenin has an ability to improve renal function and attenuates AT1R, ERK1/2-NFκB p65 signaling pathway in DNR induced nephrotoxicity in rats.

    DOI: 10.1016/j.intimp.2015.05.050

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  • Telmisartan treatment targets inflammatory cytokines to suppress the pathogenesis of acute colitis induced by dextran sulphate sodium. 国際誌

    Somasundaram Arumugam, Remya Sreedhar, Rajarajan A Thandavarayan, Vijayasree V Giridharan, Vengadeshprabhu Karuppagounder, Vigneshwaran Pitchaimani, Mst Rejina Afrin, Shizuka Miyashita, Mayumi Nomoto, Meilei Harima, Hiroshi Suzuki, Takashi Nakamura, Masahiko Nakamura, Kenji Suzuki, Kenichi Watanabe

    Cytokine   74 ( 2 )   305 - 12   2015年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The renin angiotensin system (RAS) is essential for the regulation of cardiovascular and renal functions to maintain the fluid and electrolyte homeostasis. Recent studies have demonstrated a locally expressed RAS in various tissues of mammals, which is having pathophysiological roles in those organ system. Interestingly, local RAS has important role during the inflammatory bowel disease pathogenesis. Further to delineate its role and also to identify the potential effects of telmisartan, an angiotensin receptor blocker, we have used a mouse model of acute colitis induced by dextran sulphate sodium. We have used 0.01 and 5mg/kg body weight doses of telmisartan and administered as enema to facilitate the on-site action and to reduce the systemic adverse effects. Telmisartan high dose treatment significantly reduced the disease activity index score when compared with the colitis control mice. In addition, oxidative stress and endoplasmic reticulum stress markers expression were also significantly reduced when compared with the colitis control mice. Subsequent experiments were carried out to investigate some of the mechanisms underlying its anti-inflammatory effects and identified that the mRNA levels of pro-inflammatory cytokines such as tumour necrosis factor α, interleukin 1β, interleukin 6 and monocyte chemoattractant protein 1 as well as cellular DNA damage were significantly suppressed when compared with the colitis control mice. Similarly the apoptosis marker proteins such as cleaved caspase 3 and 7 levels were down-regulated and anti-apoptotic protein Bcl2 level was significantly upregulated by telmisartan treatment. These results indicate that blockade of RAS by telmisartan can be an effective therapeutic option against acute colitis.

    DOI: 10.1016/j.cyto.2015.03.017

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  • Curcumin Decreases Renal and Liver Triglyceride Accumulation through AMPK-SREBP Signaling Pathway in Streptozotocin-induced Type 1 Diabetic Rats

    Hiroshi Suzuki, Vigneshwaran Pitchaimani, Somasundaran Arumugam, Rajarajan A. Thandavarayan, Vengadeshprabhu Karuppagounder, Remya Sreeedhar, Meilei Harima, Shizuka Miyashita, Mayumi Nomoto, Kenji Suzuki, Kenichi Watanabe, Hirohito Sone

    DIABETES   64   A146 - A146   2015年6月

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    記述言語:英語   出版者・発行元:AMER DIABETES ASSOC  

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  • Modulation of HMGB1 translocation and RAGE/NFκB cascade by quercetin treatment mitigates atopic dermatitis in NC/Nga transgenic mice. 国際誌

    Vengadeshprabhu Karuppagounder, Somasundaram Arumugam, Rajarajan A Thandavarayan, Vigneshwaran Pitchaimani, Remya Sreedhar, Rejina Afrin, Meilei Harima, Hiroshi Suzuki, Mayumi Nomoto, Shizuka Miyashita, Kenji Suzuki, Masahiko Nakamura, Kenichi Watanabe

    Experimental dermatology   24 ( 6 )   418 - 23   2015年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Quercetin, glycosylated form of flavonoid compound, has potent antioxidant and anti-inflammatory properties. In this study, we have investigated the effects of quercetin on skin lesion, high-mobility group box (HMGB)1 cascade signalling and inflammation in atopic dermatitis (AD) mouse model. AD-like lesion was induced by the application of house dust mite extract to the dorsal skin of NC/Nga transgenic mouse. After AD induction, quercetin (50 mg/kg, p.o) was administered daily for 2 weeks. We evaluated dermatitis severity, histopathological changes and changes in protein expression by Western blotting for HMGB1, receptor for advanced glycation end products (RAGE), toll-like receptor (TLR)4, nuclear factor (NF)κB, nuclear factor erythroid-2-related factor (Nrf)2, kelch-like ECH-associated protein (Keap)1, extracellular signal-regulated kinase (ERK)1/2, cyclooxygenase (COX)2, tumor necrosis factor (TNF)α, interleukin (IL)-1β, IL-2Rα and other inflammatory markers in the skin of AD mice. In addition, serum levels of T helper (Th) cytokines (interferon (IFN)γ, IL-4) were measured by enzyme-linked immunosorbent assay. Quercetin treatment attenuated the development of AD-like skin lesions. Histological analysis showed that quercetin inhibited hyperkeratosis, parakeratosis, acanthosis, mast cells and infiltration of inflammatory cells. Furthermore, quercetin treatment downregulated cytoplasmic HMGB1, RAGE, nuclear p-NFκB, p-ERK1/2, COX2, TNFα, IL-1β, IL-2Rα, IFNγ and IL-4 and upregulated nuclear Nrf2. Our data demonstrated that the HMGB1/RAGE/NFκB signalling might play an important role in skin inflammation, and quercetin treatment could be a promising agent for AD by modulating the HMGB1/RAGE/NFκB signalling and induction of Nrf2 protein.

    DOI: 10.1111/exd.12685

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  • Brain Metabolic Alterations in Moderate and Severe Hypoglycemia of Mice

    Hiroshi Suzuki, Vigneshwaran Pitchaimani, Somasundaran Arumugam, Rajarajan A. Thandavarayan, Vengadeshprabhu Karuppagounder, Remya Sreeedhar, Meilei Harima, Shizuka Miyashita, Mayumi Nomoto, Kenji Suzuki, Hirohito Sone, Kenichi Watanabe

    DIABETES   64   A107 - A107   2015年6月

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    記述言語:英語   出版者・発行元:AMER DIABETES ASSOC  

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  • Pruni cortex ameliorates skin inflammation possibly through HMGB1-NFκB pathway in house dust mite induced atopic dermatitis NC/Nga transgenic mice.

    Kenichi Watanabe, Vengadeshprabhu Karuppagounder, Somasundaram Arumugam, Rajarajan A Thandavarayan, Vigneshwaran Pitchaimani, Remya Sreedhar, Rejina Afrin, Meilei Harima, Hiroshi Suzuki, Kenji Suzuki, Takashi Nakamura, Mayumi Nomoto, Shizuka Miyashita, Kyoko Fukumoto, Kazuyuki Ueno

    Journal of clinical biochemistry and nutrition   56 ( 3 )   186 - 94   2015年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Pruni cortex, the bark of Prunus jamasakura Siebold ex Koidzumi, has been used in the Japanese systems of medicine for many years for its anti-inflammatory, antioxidant and antitussive properties. In this study, we investigated the effect of pruni cortex on atopic dermatitis NC/Nga mouse model. Atopic dermatitis-like lesion was induced by the application of house dust mite extract to the dorsal skin. After induction of atopic dermatitis, pruni cortex aqueous extract (1 g/kg, p.o.) was administered daily for 2 weeks. We evaluated dermatitis severity, histopathological changes and cellular protein expression by Western blotting for nuclear and cytoplasmic high mobility group box 1, receptor for advanced glycation end products, nuclear factor κB, apoptosis and inflammatory markers in the skin of atopic dermatitis mice. The clinical observation confirmed that the dermatitis score was significantly lower when treated with pruni cortex than in the atopic dermatitis group. Similarly pruni cortex inhibited hypertrophy and infiltration of inflammatory cells as identified by histopathology. In addition, pruni cortex significantly inhibited the protein expression of cytoplasmic high mobility group box 1, receptor for advanced glycation end products, nuclear p-nuclear factor kappa B, apoptosis and inflammatory markers. These results indicate that pruni cortex may have therapeutic potential in the treatment of atopic dermatitis by attenuating high mobility group box 1 and inflammation possibly through the nuclear factor κB pathway.

    DOI: 10.3164/jcbn.14-75

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  • Resveratrol attenuates HMGB1 signaling and inflammation in house dust mite-induced atopic dermatitis in mice. 国際誌

    Vengadeshprabhu Karuppagounder, Somasundaram Arumugam, Rajarajan A Thandavarayan, Vigneshwaran Pitchaimani, Remya Sreedhar, Rejina Afrin, Meilei Harima, Hiroshi Suzuki, Mayumi Nomoto, Shizuka Miyashita, Kenji Suzuki, Kenichi Watanabe

    International immunopharmacology   23 ( 2 )   617 - 23   2014年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Resveratrol is a polyphenol abundantly found in red grape skin and is effective against antiaging and anti-inflammation associated with immune responses. In this study, we have investigated the effect of resveratrol on skin lesion, high mobility group box (HMGB)1 and inflammation pathway in an atopic dermatitis (AD) mouse model. AD-like lesion was induced by the application of house dust mite extract to the dorsal skin of NC/Nga mouse. After AD induction, resveratrol (20 mg/kg, p.o.) was administered daily for 2 weeks. We evaluated dermatitis severity, histopathological changes, serum levels of T helper (Th) cytokines (interferon (IFN)γ, interleukin (IL)-4) and changes in protein expression by Western blotting for HMGB1, receptor for advanced glycation end products (RAGE), toll like receptor (TLR)4, nuclear factor (NF)κB, phosphatidylinositide 3-kinase (PI3K), extracellular signal-regulated kinase (ERK)1/2, cyclooxygenase (COX)2, tumor necrosis factor (TNF)α, IL-1β, IL-2Rα and other inflammatory markers in the skin of AD mice. Treatment of resveratrol inhibited the development of the AD-like skin lesions. Histological analysis showed that resveratrol inhibited hypertrophy, intracellular edema, mast cells and infiltration of inflammatory cells. Furthermore, resveratrol treatment down-regulated HMGB1, RAGE, p-NFκB, p-PI3K, p-ERK1/2, COX2, TNFα, IL-1β, IL-2Rα, IFNγ and IL-4. Considering all these findings together, the HMGB1 pathway might be a potential therapeutic target in skin inflammation, and resveratrol treatment could have beneficial effects on AD by modulating the HMGB1 protein expression.

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  • Fasting mediated increase in p-BAD(ser155) and p-AKT(ser473) in the prefrontal cortex of mice. 国際誌

    Vigneshwaran Pitchaimani, Somasundaram Arumugam, Rajarajan Amirthalingam Thandavarayan, Vengadeshprabhu Karuppagounder, Remya Sreedhar, Rejina Afrin, Meilei Harima, Hiroshi Suzuki, Shizuka Miyashita, Mayumi Nomoto, Hirohito Sone, Kenji Suzuki, Kenichi Watanabe

    Neuroscience letters   579   134 - 9   2014年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BAD-deficient mice and fasting have several common functional roles in seizures, beta-hydroxybutyrate (BHB) uptake in brain and alteration in counterregulatory hormonal regulation during hypoglycemia. Neuronal specific insulin receptor knockout (NIRKO) mice display impaired counterregulatory hormonal responses during hypoglycemia. In this study we investigated the fasting mediated expression of p-BAD(ser155) and p-AKT(ser473) in different regions of brain (prefrontal cortex, hippocampus, midbrain and hypothalamus). Fasting specifically increases p-BAD(ser155) and p-AKT(ser473) in prefrontal cortex and decreases in other regions of brain. Our results suggest that fasting may increase the uptake BHB by decreasing p-BAD(ser155) in the brain during hypoglycemia except prefrontal cortex and it uncovers specific functional area of p-BAD(ser155) and p-AKT(ser473) that may regulates counter regulatory hormonal response. Overall in support with previous findings, fasting mediated hypoglycemia activates prefrontal cortex insulin signaling which influences the hypothalamic paraventricular nucleus mediated activation of sympathoadrenal hormonal responses.

    DOI: 10.1016/j.neulet.2014.07.009

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  • 乳酸醗酵酒粕による血中LDLコレステロール低下作用の解明

    研究課題/領域番号:18K14404  2018年4月 - 2021年3月

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    鈴木 浩史

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

    乳酸醗酵酒粕は、酒粕を脱アルコール化し乳酸菌による発酵を加えたものであり、味覚や匂い等から食品としての魅力に劣る酒粕を日常的に摂取できる食品に改良したものである。酒粕では、動物実験での肝機能障害抑制作用や血中コレステロール上昇抑制作用が報告されている。一方、乳酸菌でも血中コレステロール上昇抑制作用が報告されている。乳酸醗酵酒粕の成分については、既知の報告で用いられた酒粕や乳酸菌とは異なる上に、その二つを組み合わせたところでその効果については明らかとはなっていない。本研究については、日常的に摂取できる食品に改良された乳酸醗酵酒粕による肝機能障害抑制作用を証明し、そのエビデンスを確立することを目的としている。
    本研究では、乳酸醗酵酒粕を混合した特殊飼料を用いて、非アルコール性脂肪性肝炎(NASH)モデルマウスに摂取させたところ、コントロール群と比較して血中総コレステロール値の上昇抑制がみられた。まだ解析途中ではあるが、肝線維化の抑制など、NASHの進行抑制効果も期待できる可能性がある。これをさらにヒト試験でも実証できれば、血中総コレステロール値の上昇抑制およびNASHの進行抑制効果を日常的に摂取可能な食品で得られることにつながり、国民の健康に大きく寄与できるものと考える。
    乳酸醗酵酒粕がもたらす血中総コレステロール値の上昇抑制効果の機序については未だ解析段階であり、今後さらに解析を進めることによってそのエビデンスを確立していく。
    さらに、ヒト試験についても入念に計画を立てた上で実証できるように努めていく。

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