Nicotine exposure in early childhood attenuates the expression level of striatal D2R and exacerbates high-fat induced obesity in adulthood.
| Project/Area Number |
19K20116
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 59040:Nutrition science and health science-related
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| Research Institution | University of the Ryukyus |
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Principal Investigator |
Yamazaki Satoru 琉球大学, 医学(系)研究科(研究院), 客員研究員 (50622792)
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2019: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
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| Keywords | 肥満 / ニコチン / 生活習慣病 / 食習慣・摂食調節 / 脳報酬系 / 糖尿病 / 肥満症 / 食行動 / 若年期ニコチン暴露 / 脳内分子メカニズム |
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| Outline of Research at the Start |
21世紀出生児縦断調査(厚労省H29年)の結果、受動喫煙に曝された小児が肥満を来しやすいことが明らかとなり、そのメカニズム解明が期待されている。従来の齧歯類を用いた実験から若年期のニコチン暴露が脳内報酬系を介して飲酒量を増加させること(Cell Rep2018)、エピゲノムを介して脳機能に変調を来すこと(Nat Neuroscie2016)が報告されている。また動物性脂肪の過剰摂取はエピゲノムを介して報酬系機能を撹乱し動物性脂肪依存を来す(Diabetologia2018)。これらを踏まえ、本研究では若年期ニコチン暴露が成獣期の食行動、脳内報酬系、脳内エピゲノムに及ぼす影響を検討する。
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| Outline of Final Research Achievements |
In current study, we investigated the effects of nicotine exposure (NE) in early childhood on eating behavior and reward system in adulthood. As a model of NE during early childhood, C57BL / 6J male mice at 4 weeks old were implanted with an osmotic pump and administered nicotine for 2 weeks. Mice were fed a normal diet up to 9 weeks of age and a high-fat diet (HFD) from 10 weeks of age. As a model of NE during the adulthood, mice were administered nicotine between 8 and 10 weeks of age. In mice exposed nicotine during early childhood, body weight, food intake and blood glucose level under HFD during adulthood had significantly increased, and the mRNA and protein expression levels of striatal D2R, a pivotal regulator of the reward system resulting hedonic overeating, were significantly decreased. In adult NE model, these changes were not observed. In conclusion, NE in early childhood attenuated the expression level of striatal D2R and exacerbated high-fat induced obesity in adulthood.
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| Academic Significance and Societal Importance of the Research Achievements |
受動喫煙に曝された小児は成長期に肥満を来しやすいことが報告されており（厚生労働省 21世紀 出生児横断調査特別報告2017）、幼若期の環境因子と成人期の肥満症リスクの関連性を解明するライフコース研究が注目されている。本研究の結果から幼若期のニコチン暴露が報酬系機能分子群の発現レベルを変化させ成獣期の高脂肪食性肥満を増悪させる可能性が示唆された。本研究成果を基に幼若期の環境が成人期の生活習慣病のリスクを高める新規脳内分子機構が解明されれば生活習慣病の発症予防や治療に大きく貢献することが期待される。
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Report
(3 results)
Research Products
(5 results)
