Effect of matabolic changes related to disease on methylmercury toxicity

• Project/Area Number: 23659340
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Hygiene
• Research Institution: National Institute for Minamata Disease
• Principal Investigator: YAMAMOTO Megumi 国立水俣病総合研究センター, 基礎研究部, 室長 (70344421)
• Co-Investigator(Renkei-kenkyūsha): SAKAMOTO Mineshi 国立水俣病総合研究センター, 疫学研究部, 部長 (60344420) ; MIYAMOTO Atsushi 鹿児島大学, 共同獣医学部, 教授 (70219806) ; YABUKI Akira 鹿児島大学, 共同獣医学部, 准教授 (10315400)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: メチル水銀 / 糖尿病 / 肥満 / 神経毒性 / 糖尿病マウス

Research Abstract

We compared the toxic effects of methylmercury (MeHg) between normal mice (BL/6) and type 2 diabetic mice (KK-Ay) to clarify how metabolic changes associated with type 2 diabetes mellitus (T2DM) affect MeHg toxicity. In MeHg-treated KK-Ay mice, neurological symptoms and brain lesion were observed in this experimental condition. On the other hand, body weight (BW) loss and significant pathological changes were not observed in other groups of mice. Total mercury concentration in epididymal fat pad was much lower than those of other tissues such as brain, kidney, liver, spleen and pancreas.
These results indicate that body fat gain in T2DM and low mercury accumulation in adipose tissue increased MeHg concentrations in organs and enhanced toxicity in diabetic mice at the same dose of MeHg per BW. Tolerable intake of MeHg is currently evaluated based on MeHg per BW per week. It may be necessary to consider obesity with T2DM for appropriate risk management.

Research Products

• [Journal Article] Increased methylmercury toxicity related to obesity in diabetic KK-Ay mice. (2013)
  • Author(s): Yamamoto M, Yanagisawa R, Motomura E, Nakamura M, Sakamoto M, Takeya M, Eto K.
  • Journal Title: Journal of applied toxicology : JAT. Volume: Nov 15 Issue: 8 Pages: 1-1
  • DOI: 10.1002/jat.2954
  • Peer Reviewed
• [Presentation] Increased methylmercury toxicity elated to obesity in diabetic KK-Ay mice (2013)
  • Author(s): Yamamoto, M., Yanagisawa, R., Motomura, E., Nakamura, M., Sakamoto, M., Takeya, M., Eto, K
  • Organizer: ICMGP2013
  • Place of Presentation: Edinburgh, Scotland
• [Presentation] Methylmercury toxicity in KK-Ay obese type 2 diabetic mice (2013)
  • Author(s): Yamamoto, M., Yanagisawa, R., Motomura, E., Nakamura,M., Sakamoto,M., Takeya,M., Eto, K
  • Organizer: 52nd Annual Meeting of Society of Toxicology
  • Place of Presentation: San Antonio, USA
• [Presentation] Increased methylmercury toxicity related to obesity in diabetic KK-Ay mice (2013)
  • Author(s): Yamamoto, M., Yanagisawa, R., Motomura, E., Nakamura, M., Sakamoto, M., Takeya, M., Eto, K.
  • Organizer: International Conference on Mercury as a Global Pollutant (ICMGP) 2013
  • Place of Presentation: Edinburgh, Scotland
• [Presentation] Methylmercury toxicity in KK-Ay obese type 2 diabetic mice
  • Author(s): Yamamoto M, Yanagisawa R, Motomura E, Nakamura M, Sakamoto M, Takeya M, Eto K.
  • Organizer: 52nd Annual Meeting of Society of Toxicology
  • Place of Presentation: San Antonio, USA
• [Remarks]
  • URL: http://www.nimd.go.jp/kenkyu/docs/yamamoto20140100.pdf
• [Remarks] 論文紹介
  • URL: http://www.nimd.go.jp/kenkyu/docs/yamamoto20140100.pdf