[1]尚晨,龚凤英,王林杰.肥胖相关黑棘皮病的发病机制[J].国际内分泌代谢杂志,2016,36(06):416-419.[doi:10.3760/cma.j.issn.1673-4157.2016.06.15]
 Shang Chen,Gong Fengying,Wang Linjie..Pathogenesis of obesity-related acanthosisnigricans[J].International Journal of Endocrinology and Metabolism,2016,36(06):416-419.[doi:10.3760/cma.j.issn.1673-4157.2016.06.15]
点击复制

肥胖相关黑棘皮病的发病机制()
分享到:

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

卷:
36
期数:
2016年06期
页码:
416-419
栏目:
综述
出版日期:
2016-11-20

文章信息/Info

Title:
Pathogenesis of obesity-related acanthosisnigricans
作者:
尚晨龚凤英王林杰
100730 北京,中国医学科学院,北京协和医学院,北京协和医院内分泌科,国家卫生和计划生育委员会内分泌重点实验室,协和转化医学中心
Author(s):
Shang Chen Gong Fengying Wang Linjie.
Department of Endocrinology, Key Laboratory of Endocrinology of National Health and Family Planning Commission, The Centre for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical Colle
关键词:
黑棘皮病 肥胖 高胰岛素血症 胰岛素抵抗
Keywords:
Acanthosisnigricans Obesity Hyperinsulinemia Insulin resistance
DOI:
10.3760/cma.j.issn.1673-4157.2016.06.15
摘要:
黑棘皮病是肥胖患者常见的皮肤过度角化伴局部肤色加深的特征性改变,是高胰岛素血症和胰岛素抵抗的可靠皮肤标志。该病是由于循环中过量的胰岛素通过直接或间接途径激活胰岛素样生长因子-1受体(IGF-1R),促进角化细胞和成纤维细胞生长所致。近年来的研究发现,肥胖患者皮肤的慢性炎性反应、维生素D浓度减低、瘦素分泌增加、色素上皮衍生因子(PEDF)水平升高、哺乳动物雷帕霉素靶蛋白(mTOR)通路过度活化与皮肤稳态受损等,也参与了黑棘皮病的发生和发展。探讨肥胖相关黑棘皮病的发病机制可以为临床诊断和治疗提供依据。
Abstract:
Acanthosisnigricans is a disorder characterized by pigmented and hyperkeratotic skin changes, which is often seen in obesity. It is also a reliable sign of hyperinsulinemia or insulin resistance. Previous studies have revealed that high levels of insulin can result in over activation of insulin-like growth factor-1 receptor(IGF-1R)both directly and indirectly, which in turn lead to the proliferation of keratinocytes and fibroblasts. Lately, it has been found that chronic skin inflammation, decreased serum vitamin D concentration, increased leptin secretion, elevated pigment epithelium derived factor(PEDF)level, excessive activation of the mammalian target of rapamycin(mTOR)pathway as well as impairment of skin homeostasis of obese patients might also play important roles in the process of acanthosisnigricans. Undoubtedly, there would be diagnostic and therapeutic potential in clarifying the pathogenesis of obesity-related acanthosisnigricans.

参考文献/References:

[1] Phiske MM. An approach to acanthosis nigricans[J].Indian Dermatol Online J, 2014,5(3):239-249. DOI: 10.4103/2229-5178.137765.
[2] Hermanns-Lê T, Scheen A, Piérard GE. Acanthosis nigricans associated with insulin resistance: pathophysiology and management[J].Am J Clin Dermatol, 2004,5(3):199-203.
[3] Yosipovitch G, DeVore A, Dawn A. Obesity and the skin: skin physiology and skin manifestations of obesity[J].J Am Acad Dermatol, 2007,56(6):901-916. DOI:10.1016/j.jaad.2006.12.004.
[4] Copeland K, Pankratz K, Cathey V,et al. Acanthosis nigricans, insulin resistance(HOMA)and dyslipidemia among Native American children[J].J Okla State Med Assoc, 2006,99(1):19-24.
[5] Mukhtar Q, Cleverley G, Voorhees RE,et al. Prevalence of acanthosis nigricans and its association with hyperinsulinemia in New Mexico adolescents[J].J Adolesc Health, 2001,28(5):372-376.
[6] Payne KS, Rader RK, Lastra G,et al. Posterolateral neck texture(insulin neck): early sign of insulin resistance[J]. JAMA Dermatol, 2013,149(7):875-877. DOI: 10.1001/jamadermatol.2013.4054.
[7] Kobaissi HA, Weigensberg MJ, Ball GD,et al. Relation between acanthosis nigricans and insulin sensitivity in overweight Hispanic children at risk for type 2 diabetes[J].Diabetes Care, 2004,27(6):1412-1416.
[8] Wieser V, Moschen AR, Tilg H. Inflammation, cytokines and insulin resistance: a clinical perspective[J].Arch Immunol Ther Exp(Warsz), 2013,61(2):119-125. DOI: 10.1007/s00005-012-0210-1.
[9] Schilling WH, Crook MA. Cutaneous stigmata associated with insulin resistance and increased cardiovascular risk[J]. Int J Dermatol,2014,53(9):1062-1069. DOI: 10.1111/ijd.12463.
[10] Guida B, Nino M, Perrino NR,et al. The impact of obesity on skin disease and epidermal permeability barrier status[J].J Eur Acad Dermatol Venereol, 2010,24(2):191-195. DOI: 10.1111/j.1468-3083.2009.03503.x.
[11] Huang Y,Chen J,Yang J,et al. Evaluation of depressive symptoms in obese patients with or without acanthosis nigricans[J]. Hormones(Athens),2015,14(3):417-424.
[12] Hu L, Bikle DD, Oda Y. Reciprocal role of vitamin D receptor on β-catenin regulated keratinocyteproliferation and differentiation[J]. J Steroid Biochem Mol Biol, 2014,(144 Pt A):237-241. DOI: 10.1016/j.jsbmb.2013.11.002.
[13] Pálmer HG, Anjos-Afonso F, Carmeliet G,et al. The vitamin D receptor is a Wnt effector that controls hair follicle differentiationand specifies tumor type in adult epidermis[J].PLoS One, 2008,3(1):e1483. DOI: 10.1371/journal.pone.0001483.
[14] Blum M, Dallal GE, Dawson-Hughes B. Body size and serum 25 hydroxy vitamin D response to oral supplements in healthyolder adults[J]. J Am Coll Nutr, 2008,27(2):274-279.
[15] Garanty-Bogacka B, Syrenicz M, Goral J,et al. Serum 25-hydroxyvitamin D(25-OH-D)in obese adolescents[J].Endokrynol Pol, 2011,62(6):506-511.
[16] Poomthavorn P, Saowan S, Mahachoklertwattana P,et al. Vitamin D status and glucose homeostasis in obese children and adolescents living in the tropics[J].Int J Obes(Lond), 2012,36(4):491-495. DOI: 10.1038/ijo.2011.260.
[17] Slyper AH, Kashmer L, Huang WM,et al. Acanthosis nigricans, vitamin D, and insulin resistance in obese children and adolescents[J].J Pediatr Endocrinol Metab, 2014,27(11-12):1107-1111. DOI: 10.1515/jpem-2013-0465.
[18] Romo A, Benavides S. Treatment options in insulin resistance obesity-related acanthosis nigricans[J].Ann Pharmacother, 2008,42(7):1090-1094. DOI: 10.1345/aph.1K446.
[19] Atwa M, Emara A, Balata M,et al. Serum leptin, adiponectin, and resistin among adult patients with acanthosis nigricans: correlations with insulin resistance and risk factors for cardiovascular disease[J].Int J Dermatol, 2014,53(10):e410-e420. DOI: 10.1111/ijd.12340.
[20] Stallmeyer B, K?mpfer H, Podda M,et al. A novel keratinocyte mitogen: regulation of leptin and its functional receptor inskin repair[J].J Invest Dermatol, 2001,117(1):98-105. DOI:10.1046/j.0022-202x.2001.01387.x.
[21] Takahashi H, Honma M, Ishida-Yamamoto A,et al. Adiponectin and leptin modulate cell proliferation and cytokine secretion of normal human keratinocytes and T lymphocytes[J].J Dermatol Sci, 2010,59(2):143-145. DOI: 10.1016/j.jdermsci.2010.06.004.
[22] Gr?schl M, Topf HG, Kratzsch J,et al. Salivary leptin induces increased expression of growth factors in oralkeratinocytes[J].J Mol Endocrinol,2005,34(2):353-366. DOI:10.1677/jme.1.01658.
[23] Wang P, Smit E, Brouwers MC,et al. Plasma pigment epithelium-derived factor is positively associated with obesity in Caucasian subjects, in particular with the visceral fat depot[J].Eur J Endocrinol, 2008,159(6):713-718. DOI: 10.1530/EJE-08-0521.
[24] Crowe S, Wu LE, Economou C,et al. Pigment epithelium-derived factor contributes to insulin resistance in obesity[J].Cell Metab,2009,10(1):40-47.DOI: 10.1016/j.cmet.2009.06.001.
[25] Carnagarin R, Dharmarajan AM, Dass CR. PEDF-induced alteration of metabolism leading to insulin resistance[J].Mol Cell Endocrinol, 2015,401:98-104. DOI: 10.1016/j.mce.2014.11.006.
[26] Galhardo J, Hunt LP, Shield JP. Serum levels of pigment epithelium-derived factor(PEDF)are positively associated with acanthosis nigricans in obese adolescents[J].Diabet Med, 2012,29(7):e117-e120. DOI: 10.1111/j.1464-5491.2012.03592.x.
[27] Sabater M, Moreno-Navarrete JM, Ortega FJ,et al. Circulating pigment epithelium-derived factor levels are associated with insulin resistance and decrease after weight loss[J].J Clin Endocrinol Metab, 2010,95(10):4720-4728. DOI: 10.1210/jc.2010-0630.
[28] Buerger C, Richter B, Woth K, et al. Interleukin-1β interferes with epidermal homeostasis through induction of insulin resistance: implications for psoriasis pathogenesis[J].J Invest Dermatol, 2012,132(9):2206-2214. DOI: 10.1038/jid.2012.123.
[29] Jia G, Aroor AR, Martinez-Lemus LA,et al. Overnutrition, mTOR signaling, and cardiovascular diseases[J].Am J Physiol Regul Integr Comp Physiol, 2014,307(10):R1198-R1206. DOI: 010.1152/ajpregu.00262.2014.
[30] Malisiewicz B, Boehncke S, Lang V,et al. Epidermal insulin resistance as a therapeutic target in acanthosis nigricans [J].Acta Derm Venereol,2014,94(5):607-608.DOI:10.2340/00015555-1778.

相似文献/References:

[1]曹琳,杨昱,刘超.减重手术对多囊卵巢综合征的治疗作用[J].国际内分泌代谢杂志,2014,(06):415.[doi:10.3760/cma.j.issn.1673-4157.2014.06.015]
 Cao Lin,Yang Yu,Liu Chao..Therapeutic effects of bariatric surgery on polycystic ovary syndrome[J].International Journal of Endocrinology and Metabolism,2014,(06):415.[doi:10.3760/cma.j.issn.1673-4157.2014.06.015]
[2]张莎莎,孟杰杰,沈桂芬,等.肌肉生长抑制素前肽基因干预对高脂饮食诱导的肥胖小鼠脂代谢的影响[J].国际内分泌代谢杂志,2014,(06):361.[doi:10.3760/cma.j.issn.1673-4157.2014.06.001]
 Zhang Shasha*,Meng Jiejie,Shen Guifen,et al.Effects of myostatin propeptide gene intervention on dyslipidemia in high fat diet-induced obese mice[J].International Journal of Endocrinology and Metabolism,2014,(06):361.[doi:10.3760/cma.j.issn.1673-4157.2014.06.001]
[3]郝圆圆,张婷婷,袁红网,等.增食欲素干预单纯性肥胖的作用及机制[J].国际内分泌代谢杂志,2014,(05):324.[doi:10.3760/cma.j.issn.1673-4157.2014.05.010]
 Hao Yuanyuan,Zhang Tingting,Yuan Hongwang,et al.Effects of orexin on obesity and its mechanism[J].International Journal of Endocrinology and Metabolism,2014,(06):324.[doi:10.3760/cma.j.issn.1673-4157.2014.05.010]
[4]史俊奇 邹朝春.MicroRNA与肥胖[J].国际内分泌代谢杂志,2015,(05):344.[doi:DOI:10.3760/cma.j.issn.1673-4157.2015.05.014]
 Shi Junqi,Zou Chaochun..MicroRNA and obesity[J].International Journal of Endocrinology and Metabolism,2015,(06):344.[doi:DOI:10.3760/cma.j.issn.1673-4157.2015.05.014]
[5]张如意 张桦 王娇 孙嘉 陈容平 杨锐 冉建民 陈宏.超重或肥胖2型糖尿病患者糖尿病足的 患病率及相关危险因素分析[J].国际内分泌代谢杂志,2015,(06):365.[doi:DOI:10.3760/cma.j.issn.1673-4157.2015.06.002]
 Zhang Ruyi*,Zhang Hua,Wang Jiao,et al.Prevalence and risk factors for diabetic foot in overweight or obese type 2 diabetic patients[J].International Journal of Endocrinology and Metabolism,2015,(06):365.[doi:DOI:10.3760/cma.j.issn.1673-4157.2015.06.002]
[6]刘剑 吴明昊 高宇.高脂饮食影响消化系统致肥胖的机制[J].国际内分泌代谢杂志,2015,(06):402.[doi:DOI:10.3760/cma.j.issn.1673-4157.2015.06.011]
 Liu Jian*,Wu Minghao,Gao Yu..The mechanism of obesity caused by disturbance of high fat diets on gastrointestinal system[J].International Journal of Endocrinology and Metabolism,2015,(06):402.[doi:DOI:10.3760/cma.j.issn.1673-4157.2015.06.011]
[7]张琳,费雯婕,宋光耀.网膜素与代谢综合征[J].国际内分泌代谢杂志,2016,36(01):42.[doi:10.3760/cma.j.issn.1673-4157.2016.01.010]
 Zhang Lin*,Fei Wenjie,Song Guangyao..Omentin and metabolic syndrome[J].International Journal of Endocrinology and Metabolism,2016,36(06):42.[doi:10.3760/cma.j.issn.1673-4157.2016.01.010]
[8]谢绍锋,黄莉吉,王昆,等.南京市城区40岁以上人群超重、肥胖流行 特点调查分析[J].国际内分泌代谢杂志,2016,36(03):145.[doi:10.3760/cma.j.issn.1673-4157.2016.03.01]
 Xie Shaofeng*,Huang Liji,Wang Kun,et al.Epidemiological investigation of overweight and obesity in population aged 40 years or older in Nanjing City[J].International Journal of Endocrinology and Metabolism,2016,36(06):145.[doi:10.3760/cma.j.issn.1673-4157.2016.03.01]
[9]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(06):195.[doi:10.3760/cma.j.issn.1673-4157.2016.03.13]
[10]赵一璟,陈国芳,刘超.代餐饮食在肥胖和超重患者中的应用[J].国际内分泌代谢杂志,2016,36(05):323.[doi:10.3760/cma.j.issn.1673-4157.2016.05.10]
 Zhao Yijing*,Chen Guofang,Liu Chao.Application of meal replacement in obese and overweight patients[J].International Journal of Endocrinology and Metabolism,2016,36(06):323.[doi:10.3760/cma.j.issn.1673-4157.2016.05.10]

备注/Memo

备注/Memo:
基金项目:国家自然科学基金资助项目(30540036,30771026,81370898); 北京市自然科学基金资助项目(7082079); 人社部留学人员科技活动项目择优资助经费; 国家临床重点专科建设项目单位(WBYZ2011-873)
更新日期/Last Update: 2016-12-20