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Tytuł pozycji:

Improvement of obesity-associated disorders by a small-molecule drug targeting mitochondria of adipose tissue macrophages.

Tytuł :
Improvement of obesity-associated disorders by a small-molecule drug targeting mitochondria of adipose tissue macrophages.
Autorzy :
Wang, Yawei
Tang, Binlin
Long, Lei
Luo, Peng
Xiang, Wei
Li, Xueru
Wang, Huilan
Jiang, Qingzhi
Tan, Xu
Luo, Shenglin
Li, Huijuan
Wang, Ziwen
Chen, Zelin
Leng, Yu
Jiang, Zhongyong
Wang, Yang
Ma, Le
Wang, Rui
Zeng, Chunyu
Liu, Zujuan
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Temat :
ADIPOSE tissues
DRUG target
MACROPHAGES
MITOCHONDRIA
OXIDATIVE phosphorylation
Źródło :
Nature Communications; 1/4/2021, Vol. 12 Issue 1, p1-16, 16p
Czasopismo naukowe
Pro-inflammatory activation of adipose tissue macrophages (ATMs) is causally linked to obesity and obesity-associated disorders. A number of studies have demonstrated the crucial role of mitochondrial metabolism in macrophage activation. However, there is a lack of pharmaceutical agents to target the mitochondrial metabolism of ATMs for the treatment of obesity-related diseases. Here, we characterize a near-infrared fluorophore (IR-61) that preferentially accumulates in the mitochondria of ATMs and has a therapeutic effect on diet-induced obesity as well as obesity-associated insulin resistance and fatty liver. IR-61 inhibits the classical activation of ATMs by increasing mitochondrial complex levels and oxidative phosphorylation via the ROS/Akt/Acly pathway. Taken together, our findings indicate that specific enhancement of ATMs oxidative phosphorylation improves chronic inflammation and obesity-related disorders. IR-61 might be an anti-inflammatory agent useful for the treatment of obesity-related diseases by targeting the mitochondria of ATMs. Adipose tissue macrophages are central to controlling inflammation in the context of obesity. Here the authors present a new infrared dye (IR-61) that accumulates in the mitochondria of these cells resulting in anti-inflammatory effects that counter obesity-associated pathology in mice. [ABSTRACT FROM AUTHOR]
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