| Project/Area Number |
25282028
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Eating habits
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| Research Institution | Kanazawa Medical University |
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Principal Investigator |
KOYA Daisuke 金沢医科大学, 医学部, 教授 (70242980)
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| 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)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2015: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
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| 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 / たんぱく質 / メチオニン / 代謝異常 / 腎障害 / ポドサイト / 線維化 / ケト原性アミノ酸 / 骨格筋 / 代謝 / mTOR / SIRT1 |
|---|
| 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.
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