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通过mirabegron微球增强脂肪组织的棕色化

Zheming Niu¹, Staffan Hildebrand¹, Sebastian Kappes²

¹Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, Bonn, Germany.

Journal of controlled release : official journal of the Controlled Release Society

|September 15, 2024

概括

装有mirabegron (MIR) 的聚酸-co-glycolide酸 (PLGA) 微球通过诱导有益的脂肪色提供了一种新方法来对抗肥胖. 这种局部治疗激活了热源性脂肪细胞,同时最大限度地减少了心血管副作用.

科学领域:

脂肪组织生物学脂肪组织生物学
药理学药理学是指药理学的学科.
生物材料是一种生物材料.

背景情况:

热源性棕色脂肪组织 (BAT) 激活是治疗肥胖症的一个有前途的策略.
针对BAT和白脂肪组织 (WAT) 色的药理学方法受到心血管副作用的限制.

研究的目的:

开发一种局部药物递送系统,以持续激活发热脂肪细胞.
为了减轻与β-3上腺素受体 (ADRB3) 激动剂相关的心血管风险.

主要方法:

开发了装有mirabegron (MIR),一种选择性ADRB3激动剂的聚酸-co-glycolide酸 (PLGA) 微球.
在体外和体内研究中,分离的白色脂肪组织 (WAT) 和小鼠.
评估热能标志物,脂溶和心血管参数 (静脉压,心率).
在人体皮下WAT中MIR-loaded微球 (MIR-MS) 疗效的评估.

主要成果:

MIR-MS有效地激活了棕色脂肪细胞,并在白色脂肪细胞中诱导了热生成程序.
局部MIR-MS治疗通过ADRB3.3增加了WAT色标志物和脂解.
在小鼠中,MIR-MS在注射部位诱导了iWAT棕色化,与系统MIR相比,减轻了心血管风险.
在人类皮下WAT中,MIR-MS治疗增加了脂解和解蛋白1 (UCP1) 表达.

结论:

MIR-MS 作为一种有效的局部药物输送系统,用于诱导WAT棕色化.
这种方法成功地激活了在小鼠和人类组织中的热生成脂肪细胞.
MIR-MS可减轻与ADRB3激动剂全身服药相关的心血管不良影响.

关键词:

减轻心血管方面的副作用.布朗宁是什么意思布朗宁是什么意思当地的控制释放.奇迹的开始是Mirabegron.聚乙烯-co-glycolide 酸 (PLGA) 微球微球白色脂肪组织 (WAT)

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