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.

Elov16是一种微粒体酶，与12、14和16个碳的饱和脂肪酸和单不饱和脂肪酸的伸长有关。在本研究中，我建立了肝脏特异的Elovl6缺陷小鼠(LKO)，旨在阐明Elovl6在肝脏中的生理作用，并鉴定控制能量代谢和胰岛素敏感性的脂质因素。LKO小鼠降低了肝脏中硬脂酸和油酸的水平，增加了肝脏中棕榈酸和棕榈油酸的水平。与Elovl6^&lt；-/-&gt；形成对比。高脂饲料对小鼠、LKO小鼠无保护作用。然而，LKO小鼠的高蔗糖饮食导致的胰岛素敏感性高于FLOX小鼠。这些结果表明，Elovl6反应的产物通过从头生成脂肪调节肝脏胰岛素敏感性，但需要在肝外组织中抑制Elovl6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.