Evaluation of serum micro-RNA as a new biomarker for non-alcoholic fatty liver disease (NAFLD)

• Project/Area Number: 25460706
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Fujita Health University
• Principal Investigator: TERADAIRA Ryoji 藤田保健衛生大学, 医療科学部, 名誉教授 (80087668)
• Co-Investigator(Kenkyū-buntansha): OHASHI Koji 藤田保健衛生大学, 大学院保健学研究科, 教授 (60278281)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 非アルコール性脂肪肝（NAFLD） / 血清miR-122 / バイオマーカー / 臨床検査 / 非アルコール性脂肪肝 / 血清mi-RNA-１２２ / miR-122 / 血清miRNA

Outline of Final Research Achievements

We compared the utility of serum miR-122 with routine clinical chemistry at consecutive time points during the onset of NAFLD using high-fat diet (HFD)-induced NAFLD model rats.
To clarify changes in serum levels of miR-122 during development of NAFLD, experimental rats were fed a HFD for 2-10 weeks, while control rats received standard chow. Over the 10 weeks of feeding, body weight, total liver lipids, and liver and serum triacylglycerol were increased in the HFD group compared to the control group. However, no significant changes in serum alanine aminotransferase activity were observed, suggesting that NAFLD status was mild. In contrast, we observed drastic up-regulation of circulating miR-122 levels.
Circulating miR-122 level might be superior to clinical markers traditionally used to monitor hepatic disease.

Research Products

• [Journal Article] Fructose consumption induces hypomethylation of hepatic mitochondrial DNA in rats (2016)
  • Author(s): Mirai Yamazak, Eiji Munetsuna, Hiroya Yamada, Yoshitaka Ando, Genki Mizuno, Yuri Murase, Kanako Kndo, Hiroaki Ishikawa, Ryoji Teradaira, Koji Suzuki, Koji Ohashi
  • Journal Title: Life Sciences Volume: 149 Pages: 146-152
  • DOI: 10.1016/j.lfs.2016.02.020
  • Peer Reviewed / Open Access
• [Journal Article] Longitudinal study of circulating miR-122 in a rat model of non-alcoholic fatty liver disease (2015)
  • Author(s): Ｈｉｒｏｙａ Ｙａｍａｄａ， Ｋｏｊｉ Ｏｈａｓｈｉ， Koji Suzuki, Eiji Munetsuna, Yoshitake Ando, Mirai Yamazaki, Hiroaki Ishikawa, Naohiro Ichino, Rouji Teradaira, Shuji Hashimoto
  • Journal Title: Clinica Chimica Acta Volume: 446 Pages: 267-271
  • DOI: 10.1016/j.cca.2015.05.002
  • Peer Reviewed / Open Access
• [Journal Article] Maternal fructose consumption alters messenger RNA expression of hippocampal StAR, PBR, P450(11β), 11β-HSD, and 17β-HSD in rat offspring (2015)
  • Author(s): Koji Ohashi, Yoshitaka Ando, Eiji Munetsuna, Hiroya Yamada, Mirai Yamazaki, Ayuri Nagura, Nao Taromaru, Hiroaki Ishikawa, Koji Suzuki, Ryouji Teradaira
  • Journal Title: Nutrition research Volume: 35 Issue: 3 Pages: 259-264
  • DOI: 10.1016/j.nutres.2014.11.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comparison of Urinary Levels of 8-Hydroxy-2'-deoxyguanosine between Young Females with and without Depressive Symptoms during Different Menstrual Phases (2015)
  • Author(s): Tadayuki Iida, Ken Inoue, Yasuhiro Ito, Hiroaki Ishikawa, Miwa Kagiono, Ryoji Teradaira, Chiho Chikamura, Toshihide Harada, Satoko Ezoe, and Hiroshi Yatsuya
  • Journal Title: Acta Med. Okayama Volume: 69(1) Pages: 45-50
  • Peer Reviewed
• [Journal Article] High fructose consumption induces DNA methylation at PPARα and CPT1A promoter regions in the rat liver (2015)
  • Author(s): Koji Ohashi, Eiji Munetsuna, Hiroya Yamada, Yoshitaka Ando, Mirai Yamazaki, Nao Taromaru, Ayuri Nagura, Hiroaki Ishikawa, Koji Suzuki, Ryoji Teradaira, Shuji Hashimoto
  • Journal Title: Biochemical and Biophysical Research Cmmunications Volume: 468 Issue: 1-2 Pages: 185-189
  • DOI: 10.1016/j.bbrc.2015.10.134
  • Peer Reviewed / Open Access
• [Presentation] 妊娠授乳期のフルクトース過剰摂取が仔のインスリン抵抗性へ及ぼす影響 (2016)
  • Author(s): 村瀬悠理、水野元貴、山崎未来、近藤奏子、山田宏哉、宗綱栄二、石川浩章、寺平良治、鈴木康司、大橋鉱二
  • Organizer: 第26回生物試料分析科学会年次学術集会
  • Place of Presentation: 沖縄コンベンションセンター会議棟
  • Year and Date: 2016-02-20
• [Presentation] 妊娠授乳期のフルクトース過剰摂取における仔の海馬Ucp発現解析 (2016)
  • Author(s): 水野元貴、村瀬悠理、山崎未来、近藤奏子、山田宏哉、宗綱栄二、石川浩章、寺平良治、鈴木康司、大橋鉱二
  • Organizer: 第26回生物試料分析科学会年次学術集会
  • Place of Presentation: 沖縄コンベンションセンター会議棟
  • Year and Date: 2016-02-20
• [Presentation] Serum levels of miR-20a and miR-27a are associated with NAFLD in a general Japanese population: the Yakumo study (2015)
  • Author(s): Mirai Yamazaki, Koji Suzuki, Hiroya Yamada, Koji Ohashi, Naohiro Ichino, Hiroaki Ishikawa, Keisuke Osakabe, Keiko Sugimoto, Eiji Munetsuna, Genki Mizuno, Kanako Kondo, Takashi Inoue, Ryoji Teradaira
  • Organizer: IFCC-EFLM Euromedlab Paris 2015 Congress
  • Place of Presentation: Ｐａｒｉｓ
  • Year and Date: 2015-06-22
  • Int'l Joint Research
• [Presentation] Stability of HDL-miRNA for pre-analytical conditions - Effect of RNase on HDL-miRNA - (2015)
  • Author(s): Hiroaki Ishikawa, Nao Taromaru, Kanako Kondo, Mirai Yamazaki, Genki Mizuno, Hiroya Yamada, Koji Suzuki, Eiji Munetsuna, Koji Ohashi, Ryoji Teradaira
  • Organizer: IFCC-EFLM Euromedlab Paris 2015 congress
  • Place of Presentation: Paris
  • Year and Date: 2015-06-22
  • Int'l Joint Research
• [Presentation] High fructose consumption alters DNA metylation in rat liver. (2015)
  • Author(s): Koji Ohashi, Hiroya Yamada, Yoshitaka Ando, Eiji Munetsuna, Mirai Yamazaki, Genki Mizuno, Kanako Kondo, Hiroaki Ishikawa, Koji Suzuki, Ryoji Teradaira
  • Organizer: IFCC-EFLM Euromedlab Paris 2015 congress
  • Place of Presentation: Paris
  • Year and Date: 2015-06-22
  • Int'l Joint Research
• [Presentation] 住民健診受診者における血清miR-20a, miR-27a, miR-146, miR-320とNAFLDとの関連性 (2014)
  • Author(s): 山崎未来、山田宏哉、安藤嘉崇、大橋鉱二、鈴木康司、市野直浩、石川浩章、名倉鮎里、太郎丸奈央、刑部恵介、杉本恵子、井上孝、寺平良治
  • Organizer: 第61回日本臨床検査医学会学術集会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-11-22 – 2014-11-25
• [Presentation] 血清miR-197, let7d, miR-150, miR-92の動態は喫煙習慣の影響を受ける (2014)
  • Author(s): 名倉鮎里、大橋鉱二 、山田宏哉、石川浩章、鈴木康司、市野直浩、安藤嘉崇、太郎丸奈央、山崎未来、井上孝、浜島信之、寺平良治
  • Organizer: 第54回日本臨床化学会年次学術集会
  • Place of Presentation: 東京大学
  • Year and Date: 2014-09-05 – 2014-09-07
• [Presentation] 住民健診受診者における血清miR-197, miR-320, miR-150, miR-146と非アルコール性脂肪肝疾患との関連性 (2014)
  • Author(s): 山崎未来、山田宏哉、大橋鉱二、安藤嘉崇、名倉鮎里、太郎丸奈央、石川浩章、寺平良治
  • Organizer: 第9回日本臨床検査学教育学会
  • Place of Presentation: 東京都大田区産業プラザ
  • Year and Date: 2014-08-20 – 2014-08-22
• [Presentation] Association of serum level of microRNAs (miR-27a, miR-122, and miR-320) with obesity index among Japanese subjects. (2014)
  • Author(s): Yamada Hiroya, Suzuki Koji, Ichino Naohiro, Ohashi Koji, Osakabe Keisuke, Sugimoto Keiko, Ando Yoshitaka, Ishikawa Hiroaki, Teradaira Ryoji, Inoue Takashi, Hamajima Nobuyuki, Hashimoto Shuji
  • Organizer: 20th IEA World Congress of Epidemiology
  • Place of Presentation: Anchorage, USA
  • Year and Date: 2014-08-16 – 2014-08-21
• [Presentation] メタボリックシンドロームで変動する血清microRNAと喫煙習慣の関連 (2014)
  • Author(s): 名倉鮎里、大橋鉱二、山田宏哉、石川浩章、鈴木康司、市野直浩、安藤嘉崇、太郎丸奈央、山崎未来、井上 孝、寺平良治
  • Organizer: 第25回日本臨床化学会 東海・北陸支部総会、第33回臨床検査医学会東海北陸支部例会連合大会
  • Place of Presentation: 名古屋大学
  • Year and Date: 2014-08-02
• [Presentation] Associations between circulating microRNAs miR-20a or miR-27a and non-alcoholic fatty liver disease in a general Japanese population: the Yakumo study. (2014)
  • Author(s): Mirai Yamazaki, Hiroya Yamada, Yoshitaka Ando, Koji Ohashi,Koji Suzuki, Naohiro Ichino, Hiroaki Ishikawa, Nao Taromaru, Ayuri Nagura, Keisuke Osakabe, Keiko Sugimoto, Takashi Inoue, Nobuyuki Hamajima, Ryoji Teradaira
  • Organizer: IFCC (International Federation of Clinical Chemistry and Laboratory Medicine) WorldLab Istanbul 2014
  • Place of Presentation: Istanbul, Turkey
  • Year and Date: 2014-06-22 – 2014-06-26
• [Presentation] Circulating microRNAs ,miR197, let7d, miR150, miR92, is influenced by smoking status in general population. (2014)
  • Author(s): Ayuri Nagura, Hiroya Yamada, Koji Ohashi, Hiroaki Ishikawa, Koji Suzuki, Naohiro Ichino, Yoshitaka Ando, Nao Taromaru, Mirai Yamazaki, Rika Watarai, Takashi Inoue, Nobuyuki Hamajima, Ryoji Teradaira
  • Organizer: FCC (International Federation of Clinical Chemistry and Laboratory Medicine) WorldLab Istanbul 2014
  • Place of Presentation: Istanbul, Turtey
  • Year and Date: 2014-06-22 – 2014-06-26
• [Presentation] Assessment of serum miR-122 as novel biomarker for on-alcoholic fatty liver disease in rat model (2013)
  • Author(s): Akira Sawada, Koji Ohashi, Hiroya Yamada, Yoshitaka Ando, Hiroaki Ishikawa, Koji Suzuki, Naohiro Ichino, Ryoji Teradaira
  • Organizer: 13th APFCB
  • Place of Presentation: Bali
• [Presentation] Serum miR-122 as potential biomarker for non-alcoholic fatty liver (2013)
  • Author(s): Hiroya Yamada, Koji Suzuki, Naohiro Ichino, Ando Yoshitaka, Sawada Akira, Keisuke Osakabe, Keiko Sugimoto, Ohashi Koji, Teradaira Ryouji, Takashi Inoue, Nobuyuki Hamajima, Shuji Hashimoto
  • Organizer: 13th APFCB
  • Place of Presentation: Bali
• [Presentation] Association of serum miR-122 levels with BMI, visceral and subcutaneous fat. (2013)
  • Author(s): Ohashi K, Yamada H, Suzuki K, Ichino N, Ando Y, Sawada A, Ishikawa H, Teradaira R, Hashimoto S
  • Organizer: 13th APFCB
  • Place of Presentation: Bali
• [Presentation] 血清miR-122は肥満指標と関連する (2013)
  • Author(s): 山田宏哉、鈴木康司、市野直浩、安藤嘉崇、沢田章、石川浩章、大橋鉱二、寺平良治、井上孝、橋本修二
  • Organizer: 第60回日本臨床検査医学会
  • Place of Presentation: 神戸
• [Presentation] 非アルコール性脂肪肝モデルラットにおける血清microRNAの変化 (2013)
  • Author(s): 沢田章、山田宏哉、大橋鉱二、安藤嘉崇、太郎丸奈央、石川浩章、鈴木康司、市野直浩、寺平良治
  • Organizer: 第53回日本臨床化学会
  • Place of Presentation: 徳島