FXR-ApoC2通路通过促进白色脂肪组织的棕色化来激活UCP1-介导的热生成
Sang Hee Kim1, Woo Yong Park2, Beomsu Kim1
1Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea.
The Journal of biological chemistry
|January 11, 2025
概括
法尔内索伊德X受体 (FXR) 和其目标基因ApoC2对于白色脂肪组织 (WAT) 的色至关重要. 这一途径促进色脂肪生成,为代谢性疾病提供潜在的治疗策略.
科学领域:
- 代谢调节 代谢调节 代谢调节
- 脂肪组织生物学 脂肪组织生物学
- 核受体信号传递的信号
背景情况:
- 核受体FXR调节胆酸,脂质和葡萄糖的新陈代谢.
- 肝脏和小肠中的FXR激活显示出对抗肥胖和代谢疾病的潜力.
- 在脂肪组织棕色化中的FXR的作用仍然不完全理解.
研究的目的:
- 阐明FXR-ApoC2途径在白色脂肪组织 (WAT) 色中的作用.
- 调查FXR影响色脂肪细胞分化和功能的机制.
主要方法:
- 用FXR激动剂法尔内索尔进行治疗.
- 在脂肪细胞中抑制FXR和RXRα.
- 在前脂肪细胞和色脂肪细胞中,ApoC2的过度表达.
- 关键脂肪细胞和色标志物的分析 (UCP1,PGC1α,PRDM16).
主要成果:
- FXR激活上调调色脂肪细胞标记物和色脂肪细胞中的ApoC2标基因.
- 通过FXR敲击,色脂肪细胞标志物和ApoC2表达显著减少.
- 在色脂肪生成过程中,RXRα倒置没有影响FXR表达.
- ApoC2的过度表达增加了UCP1和PGC1α的表达,表明其在调解FXR效应中的作用.
结论:
- 通过FXR介导的ApoC2通路对于WAT棕色化至关重要.
- 通过ApoC2通路,FXR诱导色脂肪生成.
- 这一途径代表了治疗与WAT功能障碍相关的代谢障碍的潜在目标.
相关概念视频
Regulation of the Unfolded Protein Response
2.4K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K
The Unfolded Protein Response
4.4K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.4K
cAMP-dependent Protein Kinase Pathways
6.1K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.1K
The Extrinsic Apoptotic Pathway
6.2K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.2K
The Intrinsic Apoptotic Pathway
6.3K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.3K
NF-κB-dependent Signaling Pathway
7.2K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.2K

![Visualization and Quantification of Brown and Beige Adipose Tissues in Mice using [18F]FDG Micro-PET/MR Imaging](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F62460.jpg&w=3840&q=50)
