2023 Fiscal Year Final Research Report
Cooking oil-derived hydroxynonenal and lifestyle-related diseases
| Project/Area Number |
19H04029
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 59040:Nutrition science and health science-related
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
及川 伸二 三重大学, 医学系研究科, 准教授 (10277006)
山下 竜也 金沢大学, 先進予防医学研究センター, 准教授 (30334783)
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| Project Period (FY) |
2019-04-01 – 2024-03-31
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| Keywords | 生活習慣病 / アルツハイマー病 / 細胞死 / ヒドロキシノネナール / リソソーム / Hsp70.1 / カルパイン / カテプシン |
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| Outline of Final Research Achievements |
To elucidate the pathogenesis of lifestyle-related diseases , I focused on the implication of the lipid-peroxidation product ‘hydroxynonenal (HNE)’ for the cell degeneration/death of brain, pancreas, and liver. Since Hsp70.1 has dual role as chaperone and lysosomal membrane stabilizer, HNE-mediated oxidative injury (carbonylation) of Hsp70.1 was highlighted. As HNE is amphiphilic, it can diffuse within the cells and react with targets like senile and/or atheromatous plaques. HNE can expand lysosomal membrane injuries by facilitating ‘calpain-mediated cleavage of the carbonylated Hsp70.1’. I found implications of HNE-mediated Hsp70.1 carbonylation for both the lysosomal membrane permeabilization/rupture and the resultant cathepsin leakage for inducing cell degeneration/death. Considering the huge number of patients suffering lifestyle-related diseases, it is valuable to consider how ω-6 polyunsaturated fatty acid-rich vegetable oils is implicated for the organ disorder.
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| Free Research Field |
神経科学、栄養化学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では世界で千万人単位の人が罹患している生活習慣病であるアルツハイマー病・２型糖尿病・非アルコール性脂肪肝炎に共通する原因物質が、サラダ油の加熱時に発生するヒドロキシノネナール(HNE)である可能性が高いことを明らかにした。ヒトの病態を忠実に再現するために、げっ歯類に比べて臓器の類似性が高く、遺伝子・アミノ酸配列がヒトと９４％もの相同性を示すニホンザルを用い、HNEがもたらすHsp70.1の異常と２次的に脳・膵・肝に生じる細胞死の機序および臓器間の分子連関について検索し、生活習慣病の根本原因を究明した。本研究は揚げ物に含まれるHNEが有害であることを立証したもので、社会的貢献度が誠に高い。
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