更新于：2024-11-01

Adiponectin receptors x PPARγ x NF-κB

更新于：2024-11-01

基本信息

关联

项与 Adiponectin receptors x PPARγ x NF-κB 相关的药物

Thymol

靶点

Adiponectin receptors x NF-κB x PPARγ

作用机制

脂联素受体激动剂 [+2]

在研机构-

原研机构-

在研适应症

肥胖

非在研适应症-

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

项与 Adiponectin receptors x PPARγ x NF-κB 相关的临床试验

IRCT20191106045356N12 / Recruiting临床2/3期IIT

Evaluation of the effectiveness of Thymol vaginal cream on improving symptoms in patients with bacterial vulvovaginitis; A double-blind randomized clinical trial

开始日期2022-08-23

申办/合作机构-

IRCT20191106045356N9 / Suspended临床3期IIT

Preparation and clinical evaluation of a aloe vera and thymol buccal gel for the treatment of aphthous stomatitis: An experimental study and a double blinded randomized clinical trial

开始日期2022-04-03

申办/合作机构-

NCT05427721 / Recruiting临床2期IIT

Thymol Administration Effects on Netrin-1 Serum Concentration on Obese Patients

The prevalence of obesity in Mexico is 35.4%, and it is considered a risk factor for the development of diabetes, systemic arterial hypertension and dyslipidemia. Obesity due to the increased distribution and growth of adipose tissue creates a pro-inflammatory state induced by molecules secreted by the adipocytes themselves. Netrin-1 is a cell migration protein, which directs the recruitment, migration and entrapment of macrophages in different tissues, within adipose tissue the entrapment of macrophages induces the release of pro-inflammatory cytokines, which increase the secretion of pro-inflammatory adipokines. It has been found in high concentration in patients with obesity, insulin resistance and type 2 diabetes. Thymol is a phytopharmaceutical derived from oregano oil that has shown powerful anti-inflammatory and antioxidant effects through the stimulation of PPAR-gamma, adiponectin and inhibition of the NF-κB pathway mediated by the JNK pathway, pathways in which netrin-1 is involved in macrophage entrapment and recruitment.

开始日期2022-04-01

申办/合作机构-

100 项与 Adiponectin receptors x PPARγ x NF-κB 相关的临床结果

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100 项与 Adiponectin receptors x PPARγ x NF-κB 相关的转化医学

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0 项与 Adiponectin receptors x PPARγ x NF-κB 相关的专利（医药）

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项与 Adiponectin receptors x PPARγ x NF-κB 相关的文献（医药）

2021-05-01·Inflammation Research3区 · 医学

FOXO3a regulates lipid accumulation and adipocyte inflammation in adipocytes through autophagy

3区 · 医学

Article

作者: Zhang, Xiaoyan ; Zhang, Xuelian ; Zhang, Xuane ; Guo, Kai ; Zhou, Zunhai ; Liu, Qiang

BACKGROUNDFOXO3a is a widely studied transcription factor and plays an important role in a variety of biology. The purpose of this study was to explore the role and potential mechanism of FOXO3a on lipid accumulation and adipocyte inflammation in adipocytes through regulation of autophagy.METHODSThe obese mouse model was successfully induced by high-fat diet. SiRNA targeting FOXO3a was transfected into differentiation of 3T3-L1 adipocytes to reduce the expression of FOXO3a. The culture medium of RAW264.7 cells was added to the differentiated 3T3-L1 adipocytes to form a co-culture system. Subsequently, ELISA or AdipoRed assay was performed to measure the expression of triglyceride (TG) and cholesterol (TC) in mouse adipose tissue or differentiation of 3T3-L1 adipocytes. Adipocyte differentiation was detected by Oil Red O-staining. Ad-mCherry-GFP-LC3II was used to detect the level of autophagy in differentiation of 3T3-L1 adipocytes. Western blotting or qRT-PCR was used to detect the expression of FOXO3a, autophagy-related proteins (beclin 1, CEBPβ, PPARγ, ACC1 and KLF4), inflammatory cytokines (TNF-α, IL-1β, IL-6 and MCP1), NF-κB signal pathway-related proteins or adipokines (Adiponectin, AdipoR1 and resistin) in differentiated 3T3-L1 or RAW264.7 cells.RESULTSThe expression of FOXO3a and autophagy levels were significantly increased in visceral adipose tissue of obese mice and differentiation of 3T3-L1 adipocytes. Downregulation of FOXO3a significantly inhibited the autophagy and lipid accumulation in differentiation of 3T3-L1 adipocytes. In addition, FOXO3a knockdown significantly reduced Lipopolysaccharide (LPS)-induced inflammation and adipokines release in RAW264.7 cells treated with the culture medium of 3T3-L1 adipocytes. These above activity changes could be reversed by autophagy inducer rapamycin.CONCLUSIONFOXO3a could promote lipid accumulation and inflammation in differentiated 3T3-L1 adipocytes by targeting autophagy. Our results provide a new theoretical basis for FOXO3a to regulate obesity.

2020-06-01·PPAR Research3区 · 医学

Integrating Literature-Based Knowledge Database and Expression Data to Explore Molecular Pathways Connecting PPARG and Myocardial Infarction

3区 · 医学

ArticleOA

作者: Dong, Yan ; Cao, Rongyuan ; Kural, Kamil Can

Peroxisome proliferator-activated receptor γ (PPARG) might play a protective role in the development of myocardial infarction (MI) with limited mechanisms identified. Genes associated with both PPARG and MI were extracted from Elsevier Pathway Studio to construct the initial network. The gene expression activity within the network was estimated through a mega-analysis with eight independent expression datasets derived from Gene Expression Omnibus (GEO) to build PPARG and MI connecting pathways. After that, gene set enrichment analysis (GSEA) was conducted to explore the functional profile of the genes involved in the PPARG-driven network. PPARG demonstrated a significantly low expression in MI patients (LFC=−0.52; p<1.84e−9). Consequently, PPARG could indicatively be promoting three MI inhibitors (e.g., SOD1, CAV1, and POU5F1) and three MI-downregulated markers (e.g., ALB, ACADM, and ADIPOR2), which were deactivated in MI cases (p<0.05), and inhibit two MI-upregulated markers (RELA and MYD88), which showed increased expression levels in MI cases (p=0.0077 and 0.047, respectively). These eight genes were mainly enriched in nutrient- and cell metabolic-related pathways and functionally linked by GSEA and PPCN. Our results suggest that PPARG could protect the heart against both the development and progress of MI through the regulation of nutrient- and metabolic-related pathways.

2014-10-15·Cancer Research1区 · 医学

Adiponectin Receptor Signaling on Dendritic Cells Blunts Antitumor Immunity

1区 · 医学

Article

作者: Gao, Liquan ; Chen, Yuan ; Greenall, Michael J. ; Plant, Gareth ; Xu, Danmei ; Quan, Jianchao ; Walsh, Kenneth ; Tyrrell, Helen E.J. ; Ding, Yunchuan ; Tan, Peng H. ; Handa, Ashok I. ; Rai, Lena ; Gill, Dipender ; Xue, Shao-An ; Xue, John Z.

AbstractImmune escape is a fundamental trait of cancer. Dendritic cells (DC) that interact with T cells represent a crucial site for the development of tolerance to tumor antigens, but there remains incomplete knowledge about how DC-tolerizing signals evolve during tumorigenesis. In this study, we show that DCs isolated from patients with metastatic or locally advanced breast cancer express high levels of the adiponectin receptors AdipoR1 and AdipoR2, which are sufficient to blunt antitumor immunity. Mechanistic investigations of ligand–receptor interactions on DCs revealed novel signaling pathways for each receptor. AdipoR1 stimulated IL10 production by activating the AMPK and MAPKp38 pathways, whereas AdipoR2 modified inflammatory processes by activating the COX-2 and PPARγ pathways. Stimulation of these pathways was sufficient to block activation of NF-κB in DC, thereby attenuating their ability to stimulate antigen-specific T-cell responses. Together, our findings reveal novel insights into how DC-tolerizing signals evolve in cancer to promote immune escape. Furthermore, by defining a critical role for adiponectin signaling in this process, our work suggests new and broadly applicable strategies for immunometabolic therapy in patients with cancer. Cancer Res; 74(20); 5711–22. ©2014 AACR.