徳島大学 教育・研究者情報データベース(EDB)

1. 池田 康将([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.生理系.薬理学]/[徳島大学.医学部.医学科.病態情報医学講座.薬理学分野]/[徳島大学.医学研究科.医学専攻.病態情報医学講座]/[徳島大学.大学院医歯薬学研究部.医学域.医科学部門.生理系.薬理学])

   役割	任意
   貢献度	任意
   学籍番号	推奨

2. (英) Watanabe Hiroaki / (日) 渡邊 大晃 / (読) わたなべ ひろあき

   役割	任意
   貢献度	任意
   学籍番号	推奨	****

3. 志内 哲也

   役割	任意
   貢献度	任意
   学籍番号	推奨

4. (英) Hamano Hirofumi / (日) 濱野 裕章 / (読) はまの ひろふみ

   役割	任意
   貢献度	任意
   学籍番号	推奨	****

5. 堀ノ内 裕也

   役割	任意
   貢献度	任意
   学籍番号	推奨

6. 今西 正樹([徳島大学.大学院医歯薬学研究部.薬学域.先端薬学教育研究プロジェクト]/[徳島大学.大学院医歯薬学研究部.薬学域.薬科学部門.生命薬学系.医薬品機能生化学])

   役割	任意
   貢献度	任意
   学籍番号	推奨

7. 合田 光寛([徳島大学.大学院医歯薬学研究部.医学域.先端医学教育研究プロジェクト]/[徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.臨床薬理学])

   役割	任意
   貢献度	任意
   学籍番号	推奨

8. 座間味 義人

   役割	任意
   貢献度	任意
   学籍番号	推奨

9. 武智 研志

   役割	任意
   貢献度	任意
   学籍番号	推奨

10. 石澤 有紀(->個人[井澤 有紀])

    役割	任意
    貢献度	任意
    学籍番号	推奨

11. 宮本 理人

    役割	任意
    貢献度	任意
    学籍番号	推奨

12. 石澤 啓介([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.臨床薬理学])

    役割	任意
    貢献度	任意
    学籍番号	推奨

13. 粟飯原 賢一([徳島大学.大学院医歯薬学研究部.医学域.連携研究部門(医学域).寄附講座系(医学域).実践地域診療・医科学])

    役割	任意
    貢献度	任意
    学籍番号	推奨

14. 土屋 浩一郎([徳島大学.大学院医歯薬学研究部.薬学域.薬科学部門.生命薬学系.医薬品機能生化学]/[徳島大学.医学部.医学科.病態情報医学講座])

    役割	任意
    貢献度	任意
    学籍番号	推奨

15. 玉置 俊晃

    役割	任意
    貢献度	任意
    学籍番号	推奨

(英) Deletion of H-ferritin in macrophages alleviates obesity and diabetes induced by high-fat diet in mice

(英) Iron accumulation affects obesity and diabetes, both of which are ameliorated by iron reduction. Ferritin, an iron-storage protein, plays a crucial role in iron metabolism. H-ferritin exerts its cytoprotective action by reducing toxicity via its ferroxidase activity. We investigated the role of macrophage H-ferritin in obesity and diabetes. Conditional macrophage-specific H-ferritin (Fth, also known as Fth1) knockout (LysM-Cre Fth KO) mice were used and divided into four groups: wild-type (WT) and LysM-Cre Fth KO mice with normal diet (ND), and WT and LysM-Cre Fth KO mice with high-fat diet (HFD). These mice were analysed for characteristics of obesity and diabetes, tissue iron content, inflammation, oxidative stress, insulin sensitivity and metabolic measurements. RAW264.7 macrophage cells were used for in vitro experiments. Iron concentration reduced, and mRNA expression of ferroportin increased, in macrophages from LysM-Cre Fth KO mice. HFD-induced obesity was lower in LysM-Cre Fth KO mice than in WT mice at 12 weeks (body weight: KO 34.6 ± 5.6 g vs WT 40.1 ± 5.2 g). mRNA expression of inflammatory cytokines and infiltrated macrophages and oxidative stress increased in the adipose tissue of HFD-fed WT mice, but was not elevated in HFD-fed LysM-Cre Fth KO mice. However, WT mice fed an HFD had elevated iron concentration in adipose tissue and spleen, which was not observed in LysM-Cre Fth KO mice fed an HFD (adipose tissue [μmol Fe/g protein]: KO 1496 ± 479 vs WT 2316 ± 866; spleen [μmol Fe/g protein]: KO 218 ± 54 vs WT 334 ± 83). Moreover, HFD administration impaired both glucose tolerance and insulin sensitivity in WT mice, which was ameliorated in LysM-Cre Fth KO mice. In addition, energy expenditure, mRNA expression of thermogenic genes, and body temperature were higher in KO mice with HFD than WT mice with HFD. In vitro experiments showed that iron content was reduced, and lipopolysaccharide-induced Tnf-α (also known as Tnf) mRNA upregulation was inhibited in a macrophage cell line transfected with Fth siRNA. Deletion of macrophage H-ferritin suppresses the inflammatory response by reducing intracellular iron levels, resulting in the prevention of HFD-induced obesity and diabetes. The findings from this study highlight macrophage iron levels as a potential therapeutic target for obesity and diabetes.

1. (英) Article.ELocationID: 10.1007/s00125-020-05153-0

2. (英) Article.PublicationTypeList.PublicationType: Journal Article

3. (英) KeywordList.Keyword: Diabetes

4. (英) KeywordList.Keyword: H-ferritin

5. (英) KeywordList.Keyword: Inflammation

6. (英) KeywordList.Keyword: Iron

7. (英) KeywordList.Keyword: Macrophage

8. (英) KeywordList.Keyword: Obesity