适应性脂肪重塑和代谢平衡需要PPARγ-FGF1轴
Johan W Jonker1, Jae Myoung Suh, Annette R Atkins
1Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Nature
|April 24, 2012
概括
纤维细胞生长因子1 (FGF1) 对于脂肪组织重塑和代谢平衡至关重要. 它的PPARγ调节对于预防糖尿病和高脂肪饮食下脂肪组织功能障碍至关重要.
科学领域:
- 代谢的恒常化是代谢的恒常化.
- 脂肪组织生物学 脂肪组织生物学
- 内分泌学 在内分泌学.
背景情况:
- 在营养物质波动期间,脂肪组织重塑对于代谢平衡至关重要.
- 调节脂肪组织适应的机制尚不清楚.
- 纤维细胞生长因子1 (FGF1) 与各种生理过程有关.
研究的目的:
- 为了确定脂肪组织重塑的关键调节者,以响应营养的可用性.
- 研究FGF1在新陈代谢平衡和胰岛素敏感性中的作用.
- 阐明脂肪组织中FGF1和PPARγ之间的调节关系.
主要方法:
- 使用了FGF1淘汰赛小鼠和高脂肪饮食挑战.
- 分析了脂肪组织组织病理学,血管,炎症和脂肪细胞特征.
- 使用PPAR反应元件研究了PPARγ对FGF1的转录调节.
主要成果:
- 在高脂肪饮食中,FGF1淘汰赛小鼠表现出具有侵略性的糖尿病表型和异常的脂肪扩张.
- 缺乏FGF1导致脂肪组织的血管病理,炎症和脂肪亡.
- PPARγ通过PPAR反应元件直接调节脂肪组织中的FGF1诱导.
结论:
- PPARγFGF1轴对于维持代谢平衡和胰岛素敏感性至关重要.
- FGF1在脂肪组织适应饮食挑战方面发挥着至关重要的作用.
- PPARγFGF1通路的失调有助于饮食诱导的代谢疾病.
相关概念视频
TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
cAMP-dependent Protein Kinase Pathways
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,...
Regulation of Food Intake
Short-term regulation of food intake primarily involves neural signals from the gastrointestinal (GI) tract, blood nutrient levels, and GI tract hormones. Communication between the gut and brain via vagal nerve fibers plays a significant role in evaluating the contents of the gut. Clinical studies have shown that protein ingestion produces a more prolonged response in these nerve fibers compared to an equivalent amount of glucose. Additionally, the activation of stretch receptors caused by GI...
Regulation of Metabolism
Cellular needs and conditions vary from cell to cell and change within individual cells over time. For example, the required enzymes and energetic demands of stomach cells are different from those of fat storage cells, skin cells, blood cells, and nerve cells. Furthermore, a digestive cell works much harder to process and break down nutrients during the time that closely follows a meal compared with many hours after a meal. As these cellular demands and conditions vary, so do the amounts and...
Global Regulatory Systems
Global regulatory systems in bacteria enable rapid and coordinated responses to environmental changes by integrating sensory inputs with gene expression, ensuring efficient adaptation to fluctuating conditions. Key global regulatory mechanisms include regulons, two-component systems, sigma factors, and secondary messengers.Regulons and Global RegulatorsA regulon is a collection of genes and operons controlled by a common global regulator. These regulators enable bacteria to prioritize resource...


