Elucidation of the mechanism involved in energy metabolic regulation by heparan sulfate

硫酸乙酰肝素能量代谢调节机制的阐明

• 批准号: 22590296
• 负责人: NAGAI Naoko
• 金额: $ 2.91万
• 依托单位: Aichi Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590296/
• 关键词: 糖鎖生物学; 代謝; ヘパラン硫酸; Hs6st2; FGF21; 褐色脂肪細胞; Ucp1; エネルギー代謝; 糖鎖; 甲状腺ホルモン; 甲状腺; 褐色脂肪組織

Heparan sulfate (HS) is a glycosaminoglycan chain which localizes extracellulary where it plays important roles in various biological processes. Heparan sulfate 6-O-sulfotransferase-2 (Hs6st2) is one of the enzymes that add sulfate groups to HS. Here we report that male Hs6st2 knockout mice showed reduced energy metabolism. Thus, 6-O-sulfation in HS seems to play an important role in mediating energy metabolism and alteration of the HS composition may result in metabolic syndrome phenotypes. Heparan sulfate 6-O-sulfation was reduced in brown adipose tissue, a major tissue regulating energy metabolism. When cultures of brown adipocytes from wild type and Hs6st2 knockout mice isolated and differentiated in vitro were treated with FGF21, downstream signaling was reduced. The serum level of thyroid stimulating hormone was significantly higher, and that of thyroxin was lower in the knockout mice, suggesting hypothyroid phenotype.

硫酸乙酰肝素 (HS) 是一种位于细胞外的糖胺聚糖链，在各种生物过程中发挥着重要作用。硫酸乙酰肝素 6-O-磺基转移酶-2 (Hs6st2) 是向 HS 添加硫酸基的酶之一。在这里，我们报告雄性 Hs6st2 基因敲除小鼠表现出能量代谢降低。因此，HS 中的 6-O-硫酸化似乎在介导能量代谢中发挥着重要作用，并且 HS 组成的改变可能导致代谢综合征表型。硫酸乙酰肝素 6-O-硫酸化在棕色脂肪组织（调节能量代谢的主要组织）中减少。当用 FGF21 处理体外分离和分化的野生型和 Hs6st2 敲除小鼠的棕色脂肪细胞培养物时，下游信号传导减弱。敲除小鼠血清促甲状腺激素水平显着升高，甲状腺素水平降低，提示甲状腺功能减退表型。

项目成果

Altered Energy Expenditure in Heparan Sulfate 6-O-sulfotransferase-2 knockout mice

硫酸乙酰肝素 6-O-磺基转移酶-2 敲除小鼠能量消耗的改变

• 发表时间: 2010
• 作者: 山本隼也;萩谷至史;鎌田祥太郎;笠原忠;石井功;永井尚子
• 通讯作者: 永井尚子

生物機能モデルと新しいリソース・リサーチツール

生物功能模型和新资源和研究工具

• 发表时间: 2011
• 作者: K.Shimizu ;N. Tobisawa;T. T. Nghia;T. Namita and Y. Kato;米川博通(編集)
• 通讯作者: 米川博通(編集)

Chondroitin Sulfate Synthase-2/Chondroitin Polymerizing Factor Has Two Variants with Distinct Function

• DOI: 10.1074/jbc.m110.109553
• 发表时间: 2010-10-29
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Ogawa, Hiroyasu;Shionyu, Masafumi;Watanabe, Hideto
• 通讯作者: Watanabe, Hideto

Increased body weight in heparan sulfate6-O-sulfotransferase (Hs6st2) knockout mice

硫酸乙酰肝素 6-O-磺基转移酶 (Hs6st2) 敲除小鼠体重增加

• 发表时间: 2011
• 作者: Imada I;EF Sato et al.;永井尚子
• 通讯作者: 永井尚子

Increased body weight in heparan sulfate 6-O-sulfotransferase (Hs6st2) knockout mice

硫酸乙酰肝素 6-O-磺基转移酶 (Hs6st2) 敲除小鼠体重增加

• 发表时间: 2011
• 作者: Sakashita;E. and Endo;H.;岡本安雄;永井尚子
• 通讯作者: 永井尚子