Investigation in the pathogenesis of metabolic syndrome with in vivo molecular imaging

体内分子影像研究代谢综合征发病机制

• 批准号: 23591298
• 负责人: YAMASHITA Hiroshi
• 金额: $ 3.08万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591298/
• 关键词: メタボリックシンドローム; 生体分子イメージング; 慢性炎症; 肥満; 制御性B細胞; インターロイキン１０; 脂肪組織; 分子イメージング; 共焦点顕微鏡; メタボリック症候群; 免疫異常; リモデリング; 糖尿病

Obesity is known to induce local inflammation within adipose tissue that contributes to systemic metabolic abnormalities. We investigated the underlying mechanisms that modulate adipose inflammation. We identified Breg cells that produce interleukin-10 constitutively within adipose tissue. B cell-specific Il10 deletion enhanced adipose inflammation and insulin resistance in diet-induced obese mice, whereas adoptive transfer of adipose tissue Breg cells ameliorated those effects. Adipose environmental factors, including CXCL12 and free fatty acids, support Breg cell function, and Breg cell fraction and function were reduced in adipose tissue from obese mice and humans. Our findings indicate that adipose tissue Breg cells maintain homeostasis within adipose tissue and that Breg cell dysfunction contributes pivotally to the progression of adipose tissue inflammation in obesity and may play significant roles in the pathogenesis of metabolic syndrome.

众所周知，肥胖会导致脂肪组织中的局部炎症，从而导致全身代谢异常。我们研究了调节脂肪炎症的潜在机制。我们鉴定出在脂肪组织中产生白介素10的Breg细胞。B细胞特异性的IL10缺失增加了饮食诱导的肥胖小鼠的脂肪炎症和胰岛素抵抗，而过继转移脂肪组织Breg细胞则改善了这些影响。脂肪环境因素，包括CXCL12和游离脂肪酸，支持Breg细胞功能，肥胖小鼠和人类脂肪组织中Breg细胞比例和功能降低。我们的研究结果表明，脂肪组织Breg细胞维持脂肪组织内的动态平衡，Breg细胞功能障碍在肥胖脂肪组织炎症进展中起关键作用，并可能在代谢综合征的发病机制中发挥重要作用。

项目成果

Adipose Tissue Remodeling and Malfunctioning in Obesity Associated with Chronic Inflammation and Local Immunity

肥胖症中的脂肪组织重塑和功能障碍与慢性炎症和局部免疫相关

• 发表时间: 2012
• 作者: Nishimura S;Ngasaki M;Manabe I;Eto K;Yamashita H;Nagai R
• 通讯作者: Nagai R

In Vivo Imaging Visualizes Discoid Platelet Aggregations without Endothelium Disruption and Contribution of Inflammatory Cytokine and Integrin Signaling

体内成像可视化盘状血小板聚集，无内皮破坏以及炎症细胞因子和整合素信号传导的影响

• 发表时间: 2012
• 作者: Nishimura S;Ngasaki M;Manabe I;Eto K;Yamashita H;Nagai R
• 通讯作者: Nagai R

In Vivo Imaging Visualizes Discoid Platelet Aggregations without

体内成像可视化盘状血小板聚集体，无需

• 发表时间: 2012
• 作者: Nishimura S;Ngasaki M;Manabe I;Eto K;Nagai R
• 通讯作者: Nagai R

Adipose Natural Regulatory B Cells Negatively Control Adipose Tissue Inflammation Associated with Obesity

脂肪自然调节 B 细胞负向控制与肥胖相关的脂肪组织炎症

• 发表时间: 2013
• 作者: Nisimura S;Nagasaki M;Manabe I;Eto K;Yamashita H;Komuro I;Nagai R
• 通讯作者: Nagai R

Adipose Natural Regulatory B Cells Negatively Control Adipose Tissue Inflammation Associated with Obesity (Featured Reserach Session)

脂肪自然调节 B 细胞负向控制与肥胖相关的脂肪组织炎症（专题研究会议）

• 发表时间: 2013
• 作者: Nisimura S;Nagasaki M;Manabe I;Eto K;Yamashita H;Komuro I;Nagai R
• 通讯作者: Nagai R