Elucidation of the physiological role of fatty acid elongase Elovl6 in liver and development of new strategy for the treatment of metabolic disease

阐明脂肪酸延长酶Elovl6在肝脏中的生理作用并开发代谢性疾病治疗新策略

• 批准号: 21689025
• 负责人: MATSUZAKA Takashi
• 金额: $ 15.89万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (A)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21689025/
• 关键词: 脂肪酸; エネルギー代謝; インスリン感受性; 肥満; メタボリックシンドローム; Elovl6; 生活習慣病; 肝臓; 脂肪酸合成; 脂肪酸組成

Elovl6 is a microsomal enzyme involved in the elongation of saturated and monounsaturated fatty acids with 12, 14, and 16 carbons. In this research, I generated liver-specific Elovl6 deficient mice (LKO), and aimed to elucidate the physiological role of Elovl6 in the liver and identify the lipid factor which control energy metabolismand insulin sensitivity. LKO mice reduce stearate and oleate levels, and increases palmitate and palmitoleate levels in the liver. In contrast to Elovl6^<-/->. mice, LKO mice were not protected against HFHS diet. However, high sucrose diet-feeding in LKO mice caused higher insulin sensitivity than those of flox mice. These results suggest that products of the Elovl6 reaction through de novo lipogenesis regulates hepatic insulin sensitivity, but Elovl6 inhibition in extrahepatic tissue is required to protect mice from HFHS-induced insulin resistance.

Elovl 6是一种微粒体酶，参与具有12、14和16个碳的饱和和单不饱和脂肪酸的延伸。本研究建立了肝脏特异性Elov 16缺陷小鼠（LKO）模型，旨在阐明Elov 16在肝脏中的生理作用，并鉴定其在肝脏中控制能量代谢和胰岛素敏感性的脂质因子。LKO小鼠肝脏中硬脂酸盐和油酸盐水平降低，棕榈酸盐和棕榈油酸盐水平升高。与Elovl 6 ^<-/->相反。在LKO小鼠中，LKO小鼠不受HFHS饮食的保护。然而，高蔗糖饲料喂养LKO小鼠引起更高的胰岛素敏感性比flox小鼠。这些结果表明，通过从头脂肪生成的Elovl 6反应的产物调节肝脏胰岛素敏感性，但需要在肝外组织中抑制Elovl 6以保护小鼠免受HFHS诱导的胰岛素抵抗。

项目成果

非アルコール性脂肪性肝炎の発症・進展における脂肪酸伸長酵素Elovl6の役割

脂肪酸延伸酶Elovl6在非酒精性脂肪性肝炎发病和进展中的作用

• 发表时间: 2009
• 作者: 松坂賢;島野仁;渥美綾香;山田信博
• 通讯作者: 山田信博

TFE3 regulates muscle metabolic gene expression, increases glycogen stores, and enhances insulin sensitivity in mice

• DOI: 10.1152/ajpendo.00204.2011
• 发表时间: 2012-04-01
• 期刊: AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
• 影响因子: 5.1
• 作者: Iwasaki, Hitoshi;Naka, Ayano;Shimano, Hitoshi
• 通讯作者: Shimano, Hitoshi

A novel bile salt sequestering agent_PEGylated and quaternized polyamine nanogel reduces VLDLand LDL cholesterol, raises HDL cholesterol, and prevents atherosclerosis in mice

新型胆盐螯合剂_聚乙二醇季化聚胺纳米凝胶降低VLDL和LDL胆固醇，升高HDL胆固醇，预防小鼠动脉粥样硬化

• 发表时间: 2011
• 作者: Rie Matsumori;Takashi Matsuzaka;Yukio Nagasaki;Hitoshi Shimano;et al
• 通讯作者: et al

Inhibition of Ubiquitin Ligase F-box and WD Repeat Domain-containing 7α (Fbw7α) Causes Hepatosteatosis through Kruppel-like Factor 5 (KLF5)/Peroxisome Proliferator-activated Receptor γ2 (PPARγ2) Pathway but Not SREBP-1c Protein in Mice

• DOI: 10.1074/jbc.m111.235283
• 发表时间: 2011-11-25
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Kumadaki, Shin;Karasawa, Tadayoshi;Shimano, Hitoshi
• 通讯作者: Shimano, Hitoshi

"PEGylated and quatemized polyamine nanogel", a brand-new bile acid sequestrant, ameliorates lipoprotein profiles and reduces atherosclerosis in low-density-lipoprotein receptor deficient and apolipoprotein E deficient mice

“聚乙二醇化和季铵化聚胺纳米凝胶”是一种全新的胆汁酸螯合剂，可改善低密度脂蛋白受体缺陷和载脂蛋白 E 缺陷小鼠的脂蛋白分布并减少动脉粥样硬化

• 发表时间: 2012
• 作者: Rie Matsumori;Takashi Matsuzaka;Yukio Nagasaki;Hitoshi Shimano;et al.
• 通讯作者: et al.