Mammalian autophagy is essential for hepatic and renal ketogenesis during starvation.

• Project/Area Number: 25860746
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Shiga University of Medical Science
• Principal Investigator: MOTOYUKI KONDO 滋賀医科大学, 医学部, 客員助教 (60569052)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: オートファジー / ケトン体 / 飢餓応答 / ケトン体新生 / 糖新生 / ケトン産生 / ケトン

Outline of Final Research Achievements

We analysed starvation induced gluconeogenesis and ketogenesis in mouse strains lacking autophagy in liver, skeletal muscle or kidney. Though skeletal muscle and kidney specific autophagy deficiency did not alter starvation induced increases in blood ketone levels, liver specific autophagy deficiency significantly attenuated this effect. During starvation, mice lacking autophagy both in liver and kidney showed even lower blood ketone levels and physical activity than mice lacking autophagy only in liver. Starvation induced massive lipid droplet formation in extra adipose tissues, which was essential for ketogenesis. Moreover, this process was impaired in the autophagy deficient liver and kidney. These findings demonstrate that hepatic and renal autophagy are essential for starvation induced lipid droplet formation and subsequent ketogenesis and, ultimately, for maintaining systemic energy homeostasis.

Research Products

• [Journal Article] Mammalian autophagy is essential for hepatic and renal ketogenesis during starvation (2016)
  • Author(s): AyanoTakagi, Shinji Kume, Motoyuki Kondo, Jun Nakazawa, MasamiChin-Kanasaki, HisazumiAraki1, Shin-ichiAraki, Daisuke Koya, Masakazu Haneda, TokuhiroChano, Taiji Matsusaka, Kenji Nagao, YusukeAdachi, LawrenceChan, Hiroshi Maegawa, Takashi Uzu
  • Journal Title: Scientific Reports Volume: 6 Pages: 18944-18944
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] The role of starvation-induced autophagy in gluconeogenesis and ketogenesis (2014)
  • Author(s): 近藤 基之
  • Organizer: EASD (European Association for the Study of Diabetes) Annual Meeting
  • Place of Presentation: Vienna Austria
  • Year and Date: 2014-09-15 – 2014-09-19