ACE2/Ang(1-7)对小鼠脂肪组织脂肪合成的影响

doi:10.3969/j.issn.1006-7795.2018.04.009

首都医科大学学报 ›› 2018, Vol. 39 ›› Issue (4): 527-531.doi: 10.3969/j.issn.1006-7795.2018.04.009

• 糖尿病合并症的基础与临床研究 • 上一篇下一篇

ACE2/Ang(1-7)对小鼠脂肪组织脂肪合成的影响

马池发¹, 史婷婷^1,2, 刘敬怡^1,2, 宋丽妮^1,2, 冯建萍^1,2, 袁明霞^1,2, 杨金奎^1,2

1. 首都医科大学附属北京同仁医院内分泌科, 北京 100730;
2. 糖尿病防治研究北京市重点实验室, 北京 100730

收稿日期:2018-06-04 出版日期:2018-07-21 发布日期:2018-07-21
通讯作者: 袁明霞 E-mail:yuanmx@vip.126.com
基金资助:
国家自然科学基金（81370946）

Effect of angiotensin-converting enzyme 2 and angiotensin(1-7) on lipogenesis in white adipose tissue of mice

Ma Chifa¹, Shi Tingting^1,2, Liu Jingyi^1,2, Song Lini^1,2, Feng Jianping^1,2, Yuan Mingxia^1,2, Yang Jinkui^1,2

1. Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China;
2. Beijng Key Laboratory of Diabetes Research and Care, Beijing 100730, China

Received:2018-06-04 Online:2018-07-21 Published:2018-07-21
Supported by:
This study was supported by National Natural Science Foundation of China(81370946).

摘要/Abstract

摘要： 目的探讨血管紧张素转化酶2（angiotensin-converting enzyme 2，ACE2）-血管紧张素（1-7）[angiotensin（1-7），Ang（1-7）]对小鼠脂肪组织脂肪合成的影响。方法选取雄性ACE2基因敲除模型小鼠及野生C57BL/6（wild-type，WT）对照小鼠，测体质量，计算体脂率，测定血清三酰甘油（triglycerides，TG）及总胆固醇（total cholesterol，TC）浓度，HE染色观察附睾脂肪细胞形态学变化，蛋白印记（Western blotting）法检测附睾脂肪组织脂肪合成因子乙酰辅酶A羧化酶α（acetyl-CoA carboxylase ɑ，ACCα）、脂肪酸合成酶（fatty acid synthetase，FAS）及脂肪型脂肪酸结合蛋白（adipocyte fatty acid binding protein，aP2）的表达。将雄性db/db小鼠采用数字表法随机分为3组，分别给予0.9%（质量分数）氯化钠注射液，Ang（1-7），Ang（1-7）+A779[Ang（1-7）的拮抗剂]皮下泵入干预4周。测体质量，Western blotting法检测小鼠附睾脂肪组织脂肪合成因子蛋白的表达。结果 ACE2基因敲除小鼠体脂率及血TG浓度明显高于野生对照小鼠。Western blotting法检测结果表明ACE2基因敲除小鼠附睾脂肪组织脂肪合成因子ACCα及FAS蛋白表达明显高于野生对照组。应用Ang（1-7）干预2型糖尿病db/db小鼠显著抑制其附睾脂肪组织脂肪合成因子ACCα及FAS蛋白表达，而应用Ang（1-7）拮抗剂A779拮抗了这一作用。结论 ACE2/Ang（1-7）抑制白色脂肪合成，其机制可能是通过抑制脂肪合成相关因子的表达发挥作用。6

关键词: 肾素-血管紧张素系统, 血管紧张素转化酶2, 血管紧张素(1-7), 脂肪合成

Abstract: Objective To identity the effect of angiotensin-converting enzyme 2(ACE2) and angiotensin (1-7) (Ang(1-7)) on lipogenesis in white adipose tissue of mice. Methods Male ACE2-knockout (ACE2KO) mice and C57BL/6(wild-type, WT) mice were chosen. The body weight, body fat percentage, total serum cholesterol, and triglycerides were measured. Hematoxylin and eosin staining was employed to observe the morphology changes of epididymal adipocyte. The protein expression of lipogenesis related genes including acetyl-CoA carboxylase a (ACCa), fatty acid synthetase(FAS) and adipocyte fatty acid binding protein (aP2) in epididymal adipose tissue was assayed by Western blotting. Male db/db mice were randomly divided into three groups. Mice were treated with normal saline (NS), A779[D-Ala7-Ang(1-7),Ang(1-7) antagonist], and Ang(1-7)+A779[Ang(1-7) antagonist] for 28 days using the micro-osmotic pump. The body weight was measured, and the protein expression of lipogenesis related genes in epididymal adipose tissue was assayed by Western blotting. Results The body fat percentage and serum triglycerides in ACE2KO mice were higher than those in WT mice. The protein expression of ACCa and FAS was increased in ACE2KO mice epididymal adipose tissue than control mice. In db/db mice, Ang(1-7) treatment downregulated the protein expression of ACCa and FAS in epididymal adipose tissue, A779 inhibited the effect. Conclusion ACE2/Ang (1-7) may inhibit lipogenesis in white adipose tissue by reduction of lipogenesis-related genes.

Key words: renin-angiotensin system, angiotensin-converting enzyme 2, angiotensin(1-7), lipogenesis

中图分类号:

R781.6

马池发, 史婷婷, 刘敬怡, 宋丽妮, 冯建萍, 袁明霞, 杨金奎. ACE2/Ang(1-7)对小鼠脂肪组织脂肪合成的影响[J]. 首都医科大学学报, 2018, 39(4): 527-531.

Ma Chifa, Shi Tingting, Liu Jingyi, Song Lini, Feng Jianping, Yuan Mingxia, Yang Jinkui. Effect of angiotensin-converting enzyme 2 and angiotensin(1-7) on lipogenesis in white adipose tissue of mice[J]. Journal of Capital Medical University, 2018, 39(4): 527-531.

参考文献

[1] Carlsson P O, Berne C, Jansson L. Angiotensin Ⅱ and the endocrine pancreas:effects on islet blood flow and insulin secretion in rats[J]. Diabetologia,1998,41(2):127-133.
[2] Giacchetti G, Sechi L A, Rilli S, et al. The renin-angiotensin-aldosterone system, glucose metabolism and diabetes[J]. Trends Endocrinol Metab,2005,16(3):120-126.
[3] Ailhaud G, Teboul M, Massiera F. Angiotensinogen, adipocyte differentiation and fat mass enlargement[J]. Curr Opin Clin Nutr Metab Care,2002,5(4):385-389.
[4] Engeli S, Schling P, Gorzelniak K, et al. The adipose-tissue renin-angiotensin-aldosterone system:role in the metabolic syndrome?[J]. Int J Biochem Cell Biol,2003,35(6):807-825.
[5] Gupte M, Boustany-Kari C M, Bharadwaj K, et al. ACE2 is expressed in mouse adipocytes and regulated by a high-fat diet[J]. Am J Physiol Regul Integr Comp Physiol,2008,295(3):R781-R788.
[6] Jones B H, Standridge M K, Moustaid N. Angiotensin Ⅱ increases lipogenesis in 3T3-L1 and human adipose cells[J]. Endocrinology,1997,138(4):1512-1519.
[7] Skurk T, van Harmelen V, Hauner H. Angiotensin Ⅱ stimulates the release of interleukin-6 and interleukin-8 from cultured human adipocytes by activation of NF-kappaB[J]. Arterioscler Thromb Vasc Biol,2004,24(7):1199-1203.
[8] Fruhbeck G, Gomez-Ambrosi J, Muruzabal F J, et al. The adipocyte:a model for integration of endocrine and metabolic signaling in energy metabolism regulation[J]. Am J Physiol Endocrinol Metab,2001,280(6):E827-E847.
[9] Kalupahana N S, Moustaid-Moussa N. The renin-angiotensin system:a link between obesity, inflammation and insulin resistance[J]. Obes Rev,2012,13(2):136-149.
[10] Marcus Y, Shefer G, Stern N. Adipose tissue renin-angiotensin-aldosterone system (RAAS) and progression of insulin resistance[J]. Mol Cell Endocrinol,2013,378(1-2):1-14.
[11] Goossens G H, Blaak E E, Arner P, et al. Angiotensin Ⅱ:a hormone that affects lipid metabolism in adipose tissue[J]. Int J Obes:Lond,2007,31(2):382-384.
[12] Ferrario C M, Chappell M C, Tallant E A, et al. Counterregulatory actions of angiotensin-(1-7)[J]. Hypertension,1997, 30(3 Pt 2):535-541.
[13] Liu C, Lv X H, Li H X, et al. Angiotensin-(1-7) suppresses oxidative stress and improves glucose uptake via Mas receptor in adipocytes[J]. Acta Diabetol,2012,49(4):291-299.
[14] Janke J, Engeli S, Gorzelniak K, et al. Mature adipocytes inhibit in vitro differentiation of human preadipocytes via angiotensin type 1 receptors[J]. Diabetes,2002,51(6):1699-1707.
[15] Kouyama R, Suganami T, Nishida J, et al. Attenuation of diet-induced weight gain and adiposity through increased energy expenditure in mice lacking angiotensin Ⅱ type 1a receptor[J]. Endocrinology,2005,146(8):3481-3489.
[16] Than A, Leow M K, Chen P. Control of adipogenesis by the autocrine interplays between angiotensin 1-7/Mas receptor and angiotensin Ⅱ/AT1 receptor signaling pathways[J]. J Biol Chem,2013,288(22):15520-15531.
[17] De Macedo S M, Guimarares T A, Andrade J M, et al. Angiotensin converting enzyme 2 activator (DIZE) modulates metabolic profiles in mice,decreasing lipogenesis[J].Protein Pept Lett,2015,22(4):332-340.
[18] 史婷婷,杨芳远,曹曦,等.血管紧张素转化酶2减少胰岛细胞的氧化应激及凋亡[J].首都医科大学学报,2017,38(2):151-155.

ACE2/Ang(1-7)对小鼠脂肪组织脂肪合成的影响

Effect of angiotensin-converting enzyme 2 and angiotensin(1-7) on lipogenesis in white adipose tissue of mice

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 7

编辑推荐

Metrics

本文评价

[1]	卢晶, 杨卫利, 杨芳远, 曹曦, 杨金奎. 医学研究的凿光探秘者——杨金奎教授[J]. 首都医科大学学报, 2020, 41(5): 849-853.
[2]	史婷婷, 杨芳远, 曹曦, 卢晶, 谢荣荣, 袁明霞, 杨金奎. 血管紧张素转化酶2减少胰岛细胞的氧化应激及凋亡[J]. 首都医科大学学报, 2017, 38(2): 151-155.
[3]	刘畅, 曹曦, 杨芳远, 张雪莲, 袁明霞, 杨金奎. 血管紧张素1-7降低脂肪细胞氧化应激增加脂联素表达[J]. 首都医科大学学报, 2014, 35(1): 45-50.
[4]	方红娟;杨金奎. 大鼠ACE2腺病毒载体的构建及其在INS-1细胞中的表达[J]. 首都医科大学学报, 2009, 30(4): 449-454.
[5]	史婷婷;马亚红;杨金奎. 血管紧张素1-7抑制剂对糖代谢的影响[J]. 首都医科大学学报, 2009, 30(4): 455-458.
[6]	华琦;师树英;秦俭;何士大. 急性心肌梗塞溶栓治疗中血浆心钠素与肾素系统的变化及意义[J]. 首都医科大学学报, 1996, 17(3): 211-214.
[7]	华琦;续大田;汪家瑞. 丙基硫氧嘧啶改善甲亢患者心脏及内分泌功能的疗效及意义[J]. 首都医科大学学报, 1994, 15(1): 41-44.