Alteration in nutrient sensing and metabolic diseases

2015 Fiscal Year Final Research Report

• Project/Area Number: 25282028
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Eating habits
• Research Institution: Kanazawa Medical University
• Principal Investigator: KOYA Daisuke 金沢医科大学, 医学部, 教授 (70242980)
• Co-Investigator(Kenkyū-buntansha): KITADA Munehiro 金沢医科大学, 医学部, 准教授 (40434469) ; KANASAKI Keizo 金沢医科大学, 医学部, 准教授 (60589919)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: オートファジー / カロリー制限 / たんぱく質制限 / ケイ原性アミノ酸 / 糖尿病

Outline of Final Research Achievements

High-calorie diet caused deregulation of the nutrient sensing signaling such as sirtuin-autophagy, thereby resulting in metabolic abnormalities and non-alcoholic fatty liver disease. Those metabolic abnormalities and pathological findings were improved through normalization of sirtuin-autophagy dysregulation by treatment with ketogenic amino acid load. Furthermore, in addition to the calorie restriction, protein-restricted diet intervened autophagy dysregulation in diabetic condition in the kidney, especially proximal tubular cells, resulting in advanced renal pathologies. In particular, improvement of metabolic abnormalities were accompanied by an improvement in insulin resistance, which might be due to the normalization of autophagy dysregulation in insulin sensitivity organs. In conclusion, autophagy regulation could be a crucial therapeutic strategy for metabolic unhealth and its related organ injury.

Free Research Field

糖尿病学、腎臓病学