Suppr超能文献

C1q/TNF家族成员的分子、生化及功能特性:脂肪组织选择性表达模式、PPAR-γ激动剂的调控、半胱氨酸介导的寡聚化、组合性关联及代谢功能

Molecular, biochemical and functional characterizations of C1q/TNF family members: adipose-tissue-selective expression patterns, regulation by PPAR-gamma agonist, cysteine-mediated oligomerizations, combinatorial associations and metabolic functions.

作者信息

Wong G William, Krawczyk Sarah A, Kitidis-Mitrokostas Claire, Revett Tracy, Gimeno Ruth, Lodish Harvey F

机构信息

Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.

出版信息

Biochem J. 2008 Dec 1;416(2):161-77. doi: 10.1042/BJ20081240.

Abstract

The insulin-sensitizing hormone, adiponectin, belongs to the expanding C1q/TNF (tumour necrosis factor) family of proteins. We recently identified a family of adiponectin paralogues designated as CTRP (C1q/TNF-related protein) 1-7, and in the present study describe CTRP10. In the present study, we show that CTRP1, CTRP2, CTRP3, CTRP5 and CTRP7 transcripts are expressed predominantly by adipose tissue. In contrast, placenta and eye expressed the highest levels of CTRP6 and CTRP10 transcripts respectively. Expression levels of CTRP1, CTRP2, CTRP3, CTRP6 and CTRP7 transcripts are up-regulated in 8-week-old obese (ob/ob) mice relative to lean controls. Treatment of mice with a PPAR-gamma (peroxisome-proliferator-activated receptor-gamma) agonist, rosiglitazone, increased the expression of CTRP1 and decreased CTRP6 transcript levels. All CTRPs are secreted glycoproteins when expressed in mammalian cells. CTRP1, CTRP2, CTRP3, CTRP5 and CTRP6 circulate in the blood and are potential endocrine hormones; their serum levels vary according to the sex and genetic background of mice. Importantly, serum levels of CTRP1 and CTRP6 are increased in adiponectin-null mice. Like adiponectin, all secreted CTRP proteins form trimers as their basic structural units. CTRP3, CTRP5, CTRP6 and CTRP10 trimers are further assembled into higher-order oligomeric complexes via disulfide bonding mediated by their N-terminal cysteine residues. Besides forming homo-oligomers, CTRP1/CTRP6, CTRP2/CTRP7 and adiponectin/CTRP2 are secreted as heterotrimers, thus providing a mechanism to potentially generate functionally distinct ligands. Functional characterization of one such family member, CTRP1, showed that it specifically activates Akt and p44/42-MAPK (mitogen-activated protein kinase) signalling pathways in differentiated mouse myotubes. Moreover, injection of recombinant CTRP1 into mice significantly reduced their serum glucose levels. Thus at least CTRP1 may be considered a novel adipokine. In summary, these molecular, biochemical and functional data provide an important framework to further address the physiological functions and mechanisms of the action of this family of secreted glycoproteins in normal and disease states.

摘要

胰岛素增敏激素脂联素属于不断扩展的C1q/TNF(肿瘤坏死因子)蛋白家族。我们最近鉴定出一个脂联素旁系同源物家族,命名为C1q/TNF相关蛋白(CTRP)1 - 7,并在本研究中描述了CTRP10。在本研究中,我们发现CTRP1、CTRP2、CTRP3、CTRP5和CTRP7转录本主要由脂肪组织表达。相比之下,胎盘和眼睛分别表达最高水平的CTRP6和CTRP10转录本。与瘦对照相比,8周龄肥胖(ob/ob)小鼠中CTRP1、CTRP2、CTRP3、CTRP6和CTRP7转录本的表达水平上调。用PPAR-γ(过氧化物酶体增殖物激活受体-γ)激动剂罗格列酮处理小鼠,可增加CTRP1的表达并降低CTRP6转录本水平。所有CTRP在哺乳动物细胞中表达时都是分泌型糖蛋白。CTRP1、CTRP2、CTRP3、CTRP5和CTRP6在血液中循环,是潜在的内分泌激素;它们的血清水平因小鼠的性别和遗传背景而异。重要的是,脂联素缺失小鼠中CTRP1和CTRP6的血清水平升高。与脂联素一样,所有分泌的CTRP蛋白都以三聚体作为其基本结构单元。CTRP3、CTRP5、CTRP6和CTRP10三聚体通过其N端半胱氨酸残基介导的二硫键进一步组装成高阶寡聚复合物。除了形成同型寡聚体,CTRP1/CTRP6、CTRP2/CTRP7和脂联素/CTRP2还以异源三聚体形式分泌,从而提供了一种潜在产生功能不同配体的机制。对其中一个家族成员CTRP1的功能表征表明,它在分化的小鼠肌管中特异性激活Akt和p44/42-MAPK(丝裂原活化蛋白激酶)信号通路。此外,向小鼠注射重组CTRP1可显著降低其血糖水平。因此,至少CTRP1可被视为一种新型脂肪因子。总之,这些分子、生化和功能数据为进一步研究该分泌型糖蛋白家族在正常和疾病状态下的生理功能及作用机制提供了重要框架。

相似文献

2
Adiponectin: no longer the lone soul in the fight against insulin resistance?
Biochem J. 2008 Dec 1;416(2):e7-9. doi: 10.1042/BJ20082033.
4
C1q/TNF-related protein-3 (CTRP3), a novel adipokine that regulates hepatic glucose output.
J Biol Chem. 2010 Dec 17;285(51):39691-701. doi: 10.1074/jbc.M110.180695. Epub 2010 Oct 15.
5
C1q/TNF-related protein 6 (CTRP6) links obesity to adipose tissue inflammation and insulin resistance.
J Biol Chem. 2017 Sep 8;292(36):14836-14850. doi: 10.1074/jbc.M116.766808. Epub 2017 Jul 18.
6
C1q/TNF-related protein 3 expression and effects on adipocyte differentiation of 3T3-L1 cells.
Cell Biol Int. 2017 Feb;41(2):197-203. doi: 10.1002/cbin.10674. Epub 2016 Nov 27.
7
Responses of complement C1q/tumor necrosis factor-related proteins to acute aerobic exercise.
Cytokine. 2023 Jan;161:156083. doi: 10.1016/j.cyto.2022.156083. Epub 2022 Nov 7.
8
Role of serum C1q/TNF-related protein family levels in patients with acute coronary syndrome.
Front Cardiovasc Med. 2022 Aug 19;9:967918. doi: 10.3389/fcvm.2022.967918. eCollection 2022.

引用本文的文献

1
Effects of non-surgical periodontal therapy on gingival crevicular fluid CTRP-1, TNF-α, and IL-10 levels.
Clin Oral Investig. 2025 Jun 21;29(7):345. doi: 10.1007/s00784-025-06420-3.
2
Identification of Important Diagnostic Genes in the Uterine Using Bioinformatics and Machine Learning.
Med J Islam Repub Iran. 2025 Jan 6;39:4. doi: 10.47176/mjiri.39.4. eCollection 2025.
4
Loss of CTRP10 results in female obesity with preserved metabolic health.
Elife. 2025 Mar 24;13:RP93373. doi: 10.7554/eLife.93373.
6
Role of CTRP14/C1QL1 in motor coordination and learning across the lifespan.
Physiol Behav. 2025 Mar 15;291:114799. doi: 10.1016/j.physbeh.2025.114799. Epub 2025 Jan 4.
7
Exploring CTRP6: a biomarker and therapeutic target in metabolic diseases.
Am J Physiol Endocrinol Metab. 2025 Feb 1;328(2):E139-E147. doi: 10.1152/ajpendo.00353.2024. Epub 2024 Dec 19.
9
Localization and expression of C1QTNF6 in chicken follicles and its regulatory effect on follicular granulosa cells.
Poult Sci. 2025 Jan;104(1):104538. doi: 10.1016/j.psj.2024.104538. Epub 2024 Nov 8.

本文引用的文献

1
The GLUT4 glucose transporter.
Cell Metab. 2007 Apr;5(4):237-52. doi: 10.1016/j.cmet.2007.03.006.
2
The oligomeric structure of high molecular weight adiponectin.
FEBS Lett. 2007 Mar 6;581(5):809-14. doi: 10.1016/j.febslet.2007.01.046. Epub 2007 Jan 30.
3
Brain adipocytokine action and metabolic regulation.
Diabetes. 2006 Dec;55 Suppl 2:S145-54. doi: 10.2337/db06-s018.
4
Adipose tissue-derived factors: impact on health and disease.
Endocr Rev. 2006 Dec;27(7):762-78. doi: 10.1210/er.2006-0033. Epub 2006 Oct 20.
5
Cbln1 is essential for interaction-dependent secretion of Cbln3.
Mol Cell Biol. 2006 Dec;26(24):9327-37. doi: 10.1128/MCB.01161-06. Epub 2006 Oct 9.
9
Immunophenotype of human adipose-derived cells: temporal changes in stromal-associated and stem cell-associated markers.
Stem Cells. 2006 Feb;24(2):376-85. doi: 10.1634/stemcells.2005-0234. Epub 2005 Dec 1.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验