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

2015 Fiscal Year Final Research Report

• 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
• 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

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.

Free Research Field

内分泌代謝・糖尿病