CD146 Associates with Gp130 to Control a Macrophage Pro‐inflammatory Program That Regulates the Metabolic Response to Obesity

Duan, Hongxia; Jing, Linhai; Xiang, Jianquan; Ju, Chenhui; Wu, Zhenzhen; Liu, Jingyu; Ma, Xinran; Chen, Xuehui; Liu, Zheng; Feng, Jing; Yan, Xiyun

doi:10.1002/advs.202103719

Cited by 11 publications

(1 citation statement)

References 68 publications

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“…5,6 In contrast, in the adipose tissue of lean individuals, the populations of ATMs are mainly composed of alternatively activated macrophages (M2-type anti-inflammatory macrophages), which suppress inflammation and enhance insulin sensitivity by producing anti-inflammatory cytokines such as IL-4, -10, -13, and arginase (ARG)-1. 7,8 Therefore, the imbalance between M1 and M2 ATMs plays a crucial role in regulating inflammatory responses and insulin resistance in adipose tissue in obesity. And the states of ATMs switching from M1 to M2 could be considered as an alternative therapeutic strategy for obesity-induced metabolic syndrome.…”

Section: Introductionmentioning

confidence: 99%

Large yellow tea polysaccharides ameliorate obesity-associated metabolic syndrome by promoting M2 polarization of adipose tissue macrophages

Wang,

Cheng

et al. 2023

Food Funct.

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Section: Introductionmentioning

confidence: 99%

Large yellow tea polysaccharides ameliorate obesity-associated metabolic syndrome by promoting M2 polarization of adipose tissue macrophages

Wang,

Cheng

et al. 2023

Food Funct.

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CD146 Associates with Gp130 to Control a Macrophage Pro‐inflammatory Program That Regulates the Metabolic Response to Obesity

et al. 2022

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The mechanism of obesity-related metabolic dysfunction involves the development of systemic inflammation, largely mediated by macrophages. Switching of M1-like adipose tissue macrophages (ATMs) to M2-like ATMs, a population of macrophages associated with weight loss and insulin sensitivity, is considered a viable therapeutic strategy for obesity-related metabolic syndrome. However, mechanisms for reestablishing the polarization of ATMs remain elusive. This study demonstrates that CD146 + ATMs accumulate in adipose tissue during diet-induced obesity and are associated with increased body weight, systemic inflammation, and obesity-induced insulin resistance. Inactivating the macrophage CD146 gene or antibody targeting of CD146 alleviates obesity-related chronic inflammation and metabolic dysfunction. Macrophage CD146 interacts with Glycoprotein 130 (Gp130), the common subunit of the receptor signaling complex for the interleukin-6 family of cytokines. CD146/Gp130 interaction promotes pro-inflammatory polarization of ATMs by activating JNK signaling and inhibiting the activation of STAT3, a transcription factor for M2-like polarization. Disruption of their interaction by anti-CD146 antibody or interleukin-6 steers ATMs toward anti-inflammatory polarization, thus attenuating obesity-induced chronic inflammation and metabolic dysfunction in mice. The results suggest that macrophage CD146 is an important determinant of pro-inflammatory polarization and plays a pivotal role in obesity-induced metabolic dysfunction. CD146 could constitute a novel therapeutic target for obesity complications.

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Metal‐Based Nanozymes with Multienzyme‐Like Activities as Therapeutic Candidates: Applications, Mechanisms, and Optimization Strategy

Dai

Xiong

et al. 2022

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manganese(III) oxide (Mn 2 O 3 ), and Prussian blue nanozyme (PBzyme), etc., have multienzyme-like activities, which enable either the efficient production of reactive oxygen species (ROS) to kill tumor cells and bacteria, or the clearance of ROS to reduce oxidative stress and inflammation. [9][10][11][12][13][14] These metal-based nanozymes display multiple antitumor, anti-infective, and anti-inflammatory activities, and offer promise as potential adjuvants, cotreatments, or alternatives to cytotoxic chemotherapeutics, antibiotics, and nonsteroidal anti-inflammatory drugs. [15][16][17] Most nanozymes in preclinical development have single-enzyme-like activity, and are thus limited by insufficient catalytic efficiency, restricted availability of substrate types and concentrations, and activity under single identifiable catalytic conditions. In comparison, those with multienzyme-like activities carry advantages of high catalytic efficiency via amplification or cascade reactions, adaptive responses to dissimilar catalytic conditions, multifunctionality in diverse pathological processes, and capacities to overcome the impediment of insufficient substrates via "self-provision." [18] At present, most reported nanozymes with multienzyme-like activities are metal-based, owing to their unsaturated sites from the inherent structure of metal atoms and the valence changes of the metal centers in case of transition metals. [4] In the last decade, researchers have studied catalytic effects and regulation rules and design schemes of metal-based nanozymes with multienzyme-like activities (MNMs), with goals to remarkably improve their therapeutic efficiency and broaden their range of applications. [15,[19][20][21][22][23][24][25] Previous review articles have discussed the spatial structures and catalytic mechanisms of nanozymes from the perspective of their physical properties, or have summarized the effects of a few types of nanozymes with potential medical applications. [4,6,[26][27][28][29][30][31][32] However, clinical relevance stands as the core motivator of nanozyme research. Therefore, this review concentrates on MNMs. This work focuses on the biological effects of nanozymes based on their intracellular interactions, intending to analyze mechanisms of action and potential therapeutic applications. Herein, we summarize MNMs, their impacts on pathogenesis, underlying mechanisms, potential medical Most nanozymes in development for medical applications only exhibit singleenzyme-like activity, and are thus limited by insufficient catalytic activity and dysfunctionality in complex pathological microenvironments. To overcome the impediments of limited substrate availabilities and concentrations, some metal-based nanozymes may mimic two or more activities of natural enzymes to catalyze cascade reactions or to catalyze multiple substrates simultaneously, thereby amplifying catalysis. Metal-based nanozymes with multienzyme-like activities (MNMs) may adapt to dissimilar catalytic conditions to exert different enzyme-like effects. ...

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CD146 Associates with Gp130 to Control a Macrophage Pro‐inflammatory Program That Regulates the Metabolic Response to Obesity

Cited by 11 publications

References 68 publications

Large yellow tea polysaccharides ameliorate obesity-associated metabolic syndrome by promoting M2 polarization of adipose tissue macrophages

Large yellow tea polysaccharides ameliorate obesity-associated metabolic syndrome by promoting M2 polarization of adipose tissue macrophages

CD146 Associates with Gp130 to Control a Macrophage Pro‐inflammatory Program That Regulates the Metabolic Response to Obesity

Metal‐Based Nanozymes with Multienzyme‐Like Activities as Therapeutic Candidates: Applications, Mechanisms, and Optimization Strategy

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