棕色脂肪组织通过诱导 FGF21 对寒冷和肾上腺素刺激作出反应。
Brown adipose tissue responds to cold and adrenergic stimulation by induction of FGF21.
机构信息
Department of Internal Medicine, Division of Endocrinology, Medical School, University of Patras, Patras, Greece.
出版信息
Mol Med. 2011;17(7-8):736-40. doi: 10.2119/molmed.2011.00075. Epub 2011 Feb 25.
Abstract
Fibroblast growth factor-21 (FGF21) is a pleiotropic protein involved in glucose, lipid metabolism and energy homeostasis, with main tissues of expression being the liver and adipose tissue. Brown adipose tissue (BAT) is responsible for cold-induced thermogenesis in rodents. The role of FGF21 in BAT biology has not been investigated. In the present study, wild-type C57BL/6J mice as well as a brown adipocyte cell line were used to explore the potential role of cold exposure and β3-adrenergic stimulation in the expression of FGF21 in BAT. Our results demonstrate that short-term exposure to cold, as well as β3-adrenergic stimulation, causes a significant induction of FGF21 mRNA levels in BAT, without a concomitant increase in FGF21 plasma levels. This finding opens new routes for the potential use of pharmaceuticals that could induce FGF21 and, hence, activate BAT thermogenesis.
摘要
成纤维细胞生长因子 21（FGF21）是一种具有多种功能的蛋白质，参与葡萄糖、脂质代谢和能量稳态的调节，其主要表达组织为肝脏和脂肪组织。棕色脂肪组织（BAT）负责啮齿动物的冷诱导产热。FGF21 在 BAT 生物学中的作用尚未得到研究。在本研究中，使用野生型 C57BL/6J 小鼠和棕色脂肪细胞系来探索冷暴露和β3-肾上腺素能刺激对 BAT 中 FGF21 表达的潜在作用。我们的结果表明，短期暴露于寒冷以及β3-肾上腺素能刺激会导致 BAT 中 FGF21 mRNA 水平显著诱导，而 FGF21 血浆水平没有相应增加。这一发现为可能诱导 FGF21 并激活 BAT 产热的药物的潜在用途开辟了新的途径。
相似文献
1
Brown adipose tissue responds to cold and adrenergic stimulation by induction of FGF21.棕色脂肪组织通过诱导 FGF21 对寒冷和肾上腺素刺激作出反应。
Mol Med. 2011;17(7-8):736-40. doi: 10.2119/molmed.2011.00075. Epub 2011 Feb 25.
2
Levels of β-klotho determine the thermogenic responsiveness of adipose tissues: involvement of the autocrine action of FGF21.β-klotho 的水平决定了脂肪组织的产热反应：FGF21 的自分泌作用的参与。
Am J Physiol Endocrinol Metab. 2021 Apr 1;320(4):E822-E834. doi: 10.1152/ajpendo.00270.2020. Epub 2021 Feb 22.
3
Regulation of Brown and White Adipocyte Transcriptome by the Transcriptional Coactivator NT-PGC-1α.转录共激活因子NT-PGC-1α对棕色和白色脂肪细胞转录组的调控
PLoS One. 2016 Jul 25;11(7):e0159990. doi: 10.1371/journal.pone.0159990. eCollection 2016.
4
FGF21 promotes thermogenic gene expression as an autocrine factor in adipocytes.成纤维细胞生长因子 21（FGF21）作为脂肪细胞的自分泌因子促进产热基因表达。
Cell Rep. 2021 Jun 29;35(13):109331. doi: 10.1016/j.celrep.2021.109331.
5
Loss of UCP2 impairs cold-induced non-shivering thermogenesis by promoting a shift toward glucose utilization in brown adipose tissue.UCP2 的缺失通过促进棕色脂肪组织向葡萄糖利用的转变，损害了冷诱导的非颤抖性产热。
Biochimie. 2017 Mar;134:118-126. doi: 10.1016/j.biochi.2017.01.006. Epub 2017 Jan 24.
6
An increase in murine skeletal muscle peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) mRNA in response to exercise is mediated by beta-adrenergic receptor activation.运动引起的小鼠骨骼肌过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC-1α）mRNA增加是由β-肾上腺素能受体激活介导的。
Endocrinology. 2007 Jul;148(7):3441-8. doi: 10.1210/en.2006-1646. Epub 2007 Apr 19.
7
FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis.成纤维细胞生长因子 21 调节适应性产热过程中的 PGC-1α 和白色脂肪组织的棕色化。
Genes Dev. 2012 Feb 1;26(3):271-81. doi: 10.1101/gad.177857.111.
8
Thermogenically competent nonadrenergic recruitment in brown preadipocytes by a PPARgamma agonist.过氧化物酶体增殖物激活受体γ（PPARγ）激动剂在棕色前脂肪细胞中引发产热能力的非肾上腺素能募集。
Am J Physiol Endocrinol Metab. 2008 Aug;295(2):E287-96. doi: 10.1152/ajpendo.00035.2008. Epub 2008 May 20.
9
ATF4 expression in thermogenic adipocytes is required for cold-induced thermogenesis in mice via FGF21-independent mechanisms.脂肪组织特异性转录因子 4（ATF4）在生热脂肪细胞中的表达对于通过成纤维生长因子 21（FGF21）非依赖机制诱导的冷诱导产热是必需的。
Sci Rep. 2024 Jan 18;14(1):1563. doi: 10.1038/s41598-024-52004-8.
10
Erythropoietin (EPO) ameliorates obesity and glucose homeostasis by promoting thermogenesis and endocrine function of classical brown adipose tissue (BAT) in diet-induced obese mice.促红细胞生成素（EPO）通过促进饮食诱导的肥胖小鼠经典棕色脂肪组织（BAT）的产热和内分泌功能，改善肥胖和葡萄糖稳态。
PLoS One. 2017 Mar 13;12(3):e0173661. doi: 10.1371/journal.pone.0173661. eCollection 2017.
引用本文的文献
1
Impact of cold exposure on shift working seafood handlers in Northern Norway: a comparative analysis across work shifts.寒冷暴露对挪威北部轮班作业的海产品加工工人的影响：跨轮班的比较分析
J Occup Med Toxicol. 2025 Jun 23;20(1):22. doi: 10.1186/s12995-025-00469-2.
2
Hepato-cardiac interorgan communication controls cardiac hypertrophy via combined endocrine-autocrine FGF21 signaling.肝心器官间通讯通过内分泌-自分泌联合的FGF21信号传导控制心脏肥大。
Cell Rep Med. 2025 Jun 17;6(6):102125. doi: 10.1016/j.xcrm.2025.102125. Epub 2025 May 7.
3
The secretory function of adipose tissues in metabolic regulation.脂肪组织在代谢调节中的分泌功能。
Life Metab. 2024 Jan 20;3(2):loae003. doi: 10.1093/lifemeta/loae003. eCollection 2024 Apr.
4
The Anti-Obesity Effect of Fish Oil in Diet-Induced Obese Mice Occurs via Both Decreased Food Intake and the Induction of Heat Production Genes in Brown but Not White Adipose Tissue.鱼油对饮食诱导肥胖小鼠的抗肥胖作用是通过减少食物摄入量以及诱导棕色而非白色脂肪组织中的产热基因来实现的。
Int J Mol Sci. 2024 Dec 31;26(1):302. doi: 10.3390/ijms26010302.
5
Impaired energy expenditure following exposure to either DDT or DDE in mice may be mediated by DNA methylation changes in brown adipose.小鼠接触滴滴涕（DDT）或滴滴伊（DDE）后能量消耗受损，可能是由棕色脂肪中的DNA甲基化变化介导的。
Environ Epigenet. 2024 Aug 23;10(1):dvae011. doi: 10.1093/eep/dvae011. eCollection 2024.
6
Adipokines in the Crosstalk between Adipose Tissues and Other Organs: Implications in Cardiometabolic Diseases.脂肪组织与其他器官相互作用中的脂肪因子：对心血管代谢疾病的影响
Biomedicines. 2024 Sep 19;12(9):2129. doi: 10.3390/biomedicines12092129.
7
Beyond the Cold: Activating Brown Adipose Tissue as an Approach to Combat Obesity.超越寒冷：激活棕色脂肪组织作为对抗肥胖的一种方法。
J Clin Med. 2024 Mar 28;13(7):1973. doi: 10.3390/jcm13071973.
8
Assessment of cold exposure-induced metabolic changes in mice using untargeted metabolomics.使用非靶向代谢组学评估小鼠冷暴露诱导的代谢变化。
Front Mol Biosci. 2023 Aug 31;10:1228771. doi: 10.3389/fmolb.2023.1228771. eCollection 2023.
9
Characterization of Circulating Cold Shock Proteins FGF21 and RBM3 in a Multi-Center Study of Pediatric Cardiac Arrest.在一项儿科心脏骤停多中心研究中循环冷休克蛋白FGF21和RBM3的特征分析
Ther Hypothermia Temp Manag. 2024 Jun;14(2):99-109. doi: 10.1089/ther.2023.0035. Epub 2023 Sep 5.
10
Brown adipocyte and browning thermogenesis: metabolic crosstalk beyond mitochondrial limits and physiological impacts.棕色脂肪细胞与棕色脂肪产热：超越线粒体限制的代谢串扰及其生理影响。
Adipocyte. 2023 Dec;12(1):2237164. doi: 10.1080/21623945.2023.2237164.
本文引用的文献
1
Thermogenic activation induces FGF21 expression and release in brown adipose tissue.产热激活诱导棕色脂肪组织中 FGF21 的表达和释放。
J Biol Chem. 2011 Apr 15;286(15):12983-90. doi: 10.1074/jbc.M110.215889. Epub 2011 Feb 13.
2
Brown adipose tissue activity controls triglyceride clearance.棕色脂肪组织活性控制甘油三酯清除。
Nat Med. 2011 Feb;17(2):200-5. doi: 10.1038/nm.2297. Epub 2011 Jan 23.
3
FGF21 reloaded: challenges of a rapidly growing field.FGF21 再加载：快速发展领域的挑战。
Trends Endocrinol Metab. 2011 Mar;22(3):81-6. doi: 10.1016/j.tem.2010.11.003. Epub 2010 Dec 29.
4
Research resource: Comprehensive expression atlas of the fibroblast growth factor system in adult mouse.研究资源：成年小鼠成纤维细胞生长因子系统的综合表达图谱
Mol Endocrinol. 2010 Oct;24(10):2050-64. doi: 10.1210/me.2010-0142. Epub 2010 Jul 28.
5
FGF21 is dispensable for hypothermia induced by fasting in mice.成纤维细胞生长因子21对小鼠禁食诱导的体温过低并非必需。
Neuro Endocrinol Lett. 2010;31(2):198-202.
6
Fibroblast growth factor 21 action in the brain increases energy expenditure and insulin sensitivity in obese rats.成纤维细胞生长因子 21 在大脑中的作用可增加肥胖大鼠的能量消耗和胰岛素敏感性。
Diabetes. 2010 Jul;59(7):1817-24. doi: 10.2337/db09-1878. Epub 2010 Mar 31.
7
Hepatic FGF21 expression is induced at birth via PPARalpha in response to milk intake and contributes to thermogenic activation of neonatal brown fat.肝 FGF21 表达在出生时通过 PPARalpha 被诱导，以响应奶的摄入，并有助于新生儿棕色脂肪的产热激活。
Cell Metab. 2010 Mar 3;11(3):206-12. doi: 10.1016/j.cmet.2010.02.001.
8
Acute glucose-lowering and insulin-sensitizing action of FGF21 in insulin-resistant mouse models--association with liver and adipose tissue effects.成纤维细胞生长因子 21（FGF21）在胰岛素抵抗小鼠模型中的急性降血糖和胰岛素增敏作用——与肝脏和脂肪组织作用相关。
Am J Physiol Endocrinol Metab. 2009 Nov;297(5):E1105-14. doi: 10.1152/ajpendo.00348.2009. Epub 2009 Aug 25.
9
FGF21 induces PGC-1alpha and regulates carbohydrate and fatty acid metabolism during the adaptive starvation response.成纤维细胞生长因子21在适应性饥饿反应过程中诱导过氧化物酶体增殖物激活受体γ共激活因子1α并调节碳水化合物和脂肪酸代谢。
Proc Natl Acad Sci U S A. 2009 Jun 30;106(26):10853-8. doi: 10.1073/pnas.0904187106. Epub 2009 Jun 16.
10
Cold-activated brown adipose tissue in healthy men.健康男性体内的冷激活棕色脂肪组织
N Engl J Med. 2009 Apr 9;360(15):1500-8. doi: 10.1056/NEJMoa0808718.
Zotero 插件