[1]龚凡,陆灏.IKKε调节代谢平衡及其机制[J].国际内分泌代谢杂志,2017,37(02):120-122.[doi:10.3760/cma.j.issn.1673-4157.2017.02.013]
 Gong Fan,Lu Hao..IKKε regulate energy balance and its mechanism[J].International Journal of Endocrinology and Metabolism,2017,37(02):120-122.[doi:10.3760/cma.j.issn.1673-4157.2017.02.013]
点击复制

IKKε调节代谢平衡及其机制()
分享到:

《国际内分泌代谢杂志》[ISSN:1673-4157/CN:12-1383/R]

卷:
37
期数:
2017年02期
页码:
120-122
栏目:
综述
出版日期:
2017-03-20

文章信息/Info

Title:
IKKε regulate energy balance and its mechanism
作者:
龚凡陆灏
201203 上海中医药大学附属曙光医院内分泌科
Author(s):
Gong Fan Lu Hao.
Department of Endocrinolgy,Shuguang Hospital Affiliated to Shanghai TCM Universty,Shanghai,201203 China
关键词:
IKKε 脂肪组织 炎症 能量平衡
Keywords:
IKKε Adipose tissue Inflammation Energy balance
DOI:
10.3760/cma.j.issn.1673-4157.2017.02.013
摘要:
炎性反应是连接肥胖和胰岛素抵抗的重要桥梁。肥胖相关的慢性低度炎性反应严重影响了胰岛素的敏感性。高脂饮食会激活炎性通路核因子-κB,从而导致该通路中的非经典激酶核因子-κB抑制蛋白激酶ε(IKKε)在肝脏和脂肪组织中持续激活。近期研究证明,IKKε在代谢平衡中扮演重要角色,通过基因敲除或药物抑制该激酶的表达能通过各种不同机制影响脂肪组织内热量的消耗,从而减轻体重,改善糖、脂代谢。这些研究提示:IKKε是一种与代谢平衡密切相关的炎性激酶,可能成为肥胖及代谢性疾病治疗的新靶点。
Abstract:
Inflammation provides a link between obesity and insulin resistance. Obesity is associated with chronic low-grade inflammation that negatively impacts insulin sensitivity. High-fat diet can increase the inflammation pathway nuclear factor-κB, which leads to a sustained elevation in level of the noncanonical inhibitor of nuclear factor κB kinase(IKK)ε in liver and adipose tissues. Emerging evidence suggests that IKKε plays a very important role in energy balance. IKKε knockout or the inhibitor of IKKε can elevate energy expenditure, lose weight, relieve the disorders of metabolism through different mechanisms. Thus, IKKε is a crucial kinase in metabolism and may represent an attractive therapeutic target for obesity and metabolic diseases.

参考文献/References:

[1] Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance[J].Science,1993,259(5091):87-91.DOI: 10.1126/science.7678183.
[2] Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity[J].Annu Rev Immunol,2011,29:415-445. DOI: 10.1146/annurev-immunol-031210-101322.
[3] Chen Y, Zhu J, Lum PY,et al. Variations in DNA elucidate molecular networks that cause disease[J].Nature,2008,452(7186):429-435. DOI: 10.1038/nature06757.
[4] Xu H, Barnes GT, Yang Q,et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance[J].J Clin Invest,2003,112(12):1821-1830.DOI: 10.1172/JCI19451.
[5] Verhelst K, Verstrepen L, Carpentier I,et al. IκB kinase ε(IKKε): a therapeutic target in inflammation and cancer[J].Biochem Pharmacol,2013,85(7):873-880. DOI: 10.1016/j.bcp.2013.01.007.
[6] Pasparakis M. Regulation of tissue homeostasis by NF-kappaB signalling: implications for inflammatory diseases[J].Nat Rev Immunol,2009,9(11):778-788. DOI: 10.1038/nri2655.
[7] Kravchenko VV, Mathison JC, Schwamborn K, et al. IKKi/IKKepsilon plays a key role in integrating signals induced by pro-inflammatory stimuli[J].J Biol Chem,2003,278(29):26612-26619. DOI:10.1074/jbc.M303001200.
[8] Verstrepen L, Verhelst K, Carpentier I, et al. TAX1BP1, a ubiquitin-binding adaptor protein in innate immunity and beyond[J].Trends Biochem Sci,2011,36(7):347-354. DOI: 10.1016/j.tibs.2011.03.004.
[9] Clément JF, Meloche S, Servant MJ. The IKK-related kinases: from innate immunity to oncogenesis[J].Cell Res,2008,18(9):889-899. DOI: 10.1038/cr.2008.273.
[10] Clark K, Peggie M, Plater L,et al. Novel cross-talk within the IKK family controls innate immunity[J].Biochem J,2011,434(1):93-104. DOI: 10.1042/BJ20101701.
[11] Lumeng CN, Saltiel AR. Inflammatory links between obesity and metabolic disease[J].J Clin Invest,2011,121(6):2111-2117. DOI: 10.1172/JCI57132.
[12] Chiang SH, Bazuine M, Lumeng CN,et al. The protein kinase IKKepsilon regulates energy balance in obese mice[J].Cell,2009,138(5):961-975. DOI: 10.1016/j.cell.2009.06.046.
[13] Mowers J, Uhm M, Reilly SM,et al. Inflammation produces catecholamine resistance in obesity via activation of PDE3B by the protein kinases IKKε and TBK1[J].Elife,2013,2:e01119. DOI: 10.7554/eLife.01119.
[14] Bonif M, Meuwis MA, Close P, et al. TNFalpha-and IKKbeta-mediated TANK/I-TRAF phosphorylation: implications for interaction with NEMO/IKKgamma and NF-kappaB activation[J].Biochem J,2006,394(Pt 3):593-603.DOI: 10.1042/BJ20051659.
[15] Sabio G, Das M, Mora A, et al. A stress signaling pathway in adipose tissue regulates hepatic insulin resistance[J].Science,2008,322(5907):1539-1543. DOI: 10.1126/science.1160794.
[16] Wang Y, Lu X, Zhu L,et al. IKK epsilon kinase is crucial for viral G protein-coupled receptor tumorigenesis[J].Proc Natl Acad Sci U S A,2013,110(27):11139-11144.DOI:10.1073/pnas.1219829110.
[17] Weissmann L, Quaresma PG, Santos AC,et al. IKKε is key to induction of insulin resistance in the hypothalamus, and its inhibition reverses obesity[J].Diabetes,2014,63(10):3334-3345. DOI: 10.2337/db13-1817.
[18] Reilly SM, Ahmadian M, Zamarron BF,et al. A subcutaneous adipose tissue-liver signalling axis controls hepatic gluconeogenesis[J].Nat Commun,2015,6:6047. DOI: 10.1038/ncomms7047.
[19] Wang N, Ahmed S, Haqqi TM. Genomic structure and functional characterization of the promoter region of human IkappaB kinase-related kinase IKKi/IKKvarepsilon gene[J].Gene,2005,353(1):118-133.DOI: 10.1016/j.gene.2005.04.013.

相似文献/References:

[1]赵紫琴,雒瑢,田凤石,等.替米沙坦对OLETF大鼠皮下和内脏脂肪组织PPARγ表达的影响[J].国际内分泌代谢杂志,2014,(06):365.[doi:10.3760/cma.j.issn.1673-4157.2014.06.002]
 Zhao Ziqin*,Luo Rong,Tian Fengshi,et al.Effects of telmisartan on expression of PPARγ in subcutaneous and visceral adipose tissue in OLETF rats[J].International Journal of Endocrinology and Metabolism,2014,(02):365.[doi:10.3760/cma.j.issn.1673-4157.2014.06.002]
[2]杨曦,刘玉洁,马慧娟.C1q/肿瘤坏死因子相关蛋白12与糖代谢[J].国际内分泌代谢杂志,2016,36(03):195.[doi:10.3760/cma.j.issn.1673-4157.2016.03.13]
 Yang Xi*,Liu Yujie,Ma Huijuan..C1q/tumor necrosis factor-related protein 12 and glucose metabolism[J].International Journal of Endocrinology and Metabolism,2016,36(02):195.[doi:10.3760/cma.j.issn.1673-4157.2016.03.13]
[3]徐传翀,尚文斌.脂肪固有免疫细胞与胰岛素抵抗[J].国际内分泌代谢杂志,2016,36(04):257.[doi:10.3760/cma.j.issn.1673-4157.2016.04.11]
 Xu Chuanchong,Shang Wenbin.Innate immune cells in adipose tissue and insulin resistance[J].International Journal of Endocrinology and Metabolism,2016,36(02):257.[doi:10.3760/cma.j.issn.1673-4157.2016.04.11]
[4]田清武,孙树凯,翟玉娥,等.雌激素对去卵巢大鼠内脏脂肪细胞脂肪因子表达水平的影响[J].国际内分泌代谢杂志,2016,36(06):374.[doi:10.3760/cma.j.issn.1673-4157.2016.06.04]
 Tian Qingwu*,Sun Shukai,Zhai Yue,et al.Effects of estrogen on the expression of adipokines in visceral fat cells in ovariectomized rats[J].International Journal of Endocrinology and Metabolism,2016,36(02):374.[doi:10.3760/cma.j.issn.1673-4157.2016.06.04]
[5]王艳立,张林,胡茂清.长链非编码RNAs与脂肪组织的关系[J].国际内分泌代谢杂志,2017,37(02):131.[doi:10.3760/cma.j.issn.1673-4157.2017.02.016]
 Wang Yanli*,Zhang Lin,Hu Maoqing..Relationship between long noncoding RNAs and adipose tissue[J].International Journal of Endocrinology and Metabolism,2017,37(02):131.[doi:10.3760/cma.j.issn.1673-4157.2017.02.016]
[6]高晶扬,张曼娜,曲伸.microRNA与脂肪组织慢性低度炎性反应[J].国际内分泌代谢杂志,2017,37(02):135.[doi:10.3760/cma.j.issn.1673-4157.2017.02.017]
 Gao Jingyang,Zhang Manna,Qu Shen..microRNA and chronic low-grade inflammation of adipose tissue[J].International Journal of Endocrinology and Metabolism,2017,37(02):135.[doi:10.3760/cma.j.issn.1673-4157.2017.02.017]
[7]许瀚元 朱惠娟 龚凤英.恒定自然杀伤细胞与肥胖[J].国际内分泌代谢杂志,2019,39(01):40.[doi:10.3760/cma.j.issn.1673-4157.2019.01.010]
 Xu Hanyuan,Zhu Huijuan,Gong Fengying.Invariant natural killer T cells and obesity[J].International Journal of Endocrinology and Metabolism,2019,39(02):40.[doi:10.3760/cma.j.issn.1673-4157.2019.01.010]
[8]许瀚元 朱惠娟 龚凤英.成纤维细胞生长因子1与糖脂代谢[J].国际内分泌代谢杂志,2019,39(03):190.[doi:10.3760/cma.j.issn.1673-4157.2019.03.011]
 Xu Hanyuan,Zhu Huijuan,Gong Fengying.Fibroblast growth factor 1 and glucolipid metabolism[J].International Journal of Endocrinology and Metabolism,2019,39(02):190.[doi:10.3760/cma.j.issn.1673-4157.2019.03.011]
[9]杨佳苗 沈山梅.水通道蛋白7与脂肪组织代谢的关系[J].国际内分泌代谢杂志,2019,39(04):253.[doi:10.3760/cma.j.issn.1673-4157.2019.04.009]
 Yang Jiamiao,Shen Shanmei.Association between aquaporin 7 and adipose metabolism[J].International Journal of Endocrinology and Metabolism,2019,39(02):253.[doi:10.3760/cma.j.issn.1673-4157.2019.04.009]
[10]刘雨平,罗佐杰.促甲状腺激素受体在非甲状腺组织中的表达及意义[J].国际内分泌代谢杂志,2021,41(01):10.[doi:10.3760/cma.j.cn121383-20200509-05015]
 Liu Yuping,Luo Zuojie..Expression and significance of thyroid stimulating hormone receptor in extrathyroidal tissues[J].International Journal of Endocrinology and Metabolism,2021,41(02):10.[doi:10.3760/cma.j.cn121383-20200509-05015]

备注/Memo

备注/Memo:
基金项目:国家自然科学基金资助项目(81503552); 上海市中医临床重点实验室资助项目(14DZ2273200); 上海市中医药事业发展三年行动计划项目(ZYSNXD-CC-YJXYY ZY3-CCCX-3-3041) 通信作者:陆灏,Email:luhao403@163.com
更新日期/Last Update: 2017-03-20