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作者简介:

张明军(1968-),男,安徽滁州人,副教授,博士,研究方向为运动生理学。

中图分类号:G804

文献标识码:A

文章编号:1008-3596(2017)01-0054-06

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参考文献 4
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参考文献 13
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参考文献 14
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参考文献 15
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参考文献 16
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参考文献 18
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参考文献 19
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参考文献 20
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目录contents

    摘要

    目的:研究运动对RBP4诱导的脂代谢异常鼠肝脏ACC1表达和脂肪合成的影响。方法:重组人RBP4注射建立脂代谢异常鼠模型。设一次性运动组(RBP4 One-time exercise group,ROE组)、8周有氧运动组(RBP4 aerobic exercise group,RAE组)和安静对照组(RBP4 control group,RC组)。结果:ROE组血清RBP4水平与RC组相比显著降低(P<0.05),血清TG和肝脏TG含量无显著改变(P>0.05)。RAE组血清RBP4、TG和肝脏TG含量与RC组和ROE组相比均显著降低(P<0.01)。与RC组相比,ROE组和RAE组肝脏ACC1mRNA表达均显著降低(P<0.01)。与RC组相比,ROE组ACC1蛋白表达无显著改变(P>0.05)。与RC组和ROE组相比,RAE组ACC1蛋白表达均显著降低(P<0.01)。结论:高RBP4显著增加小鼠肝脏ACC1基因和蛋白表达增加,促进肝脏脂肪合成。8周有氧运动抑制了RBP4在肝脏的脂肪合成促进作用,改善脂代谢,机制涉及降低RBP4水平、减少肝脏ACC1基因和蛋白表达以及TG的合成。

    Abstract

    Objective : To study effects of exercise on ACC1 expression and fat synthesis of liver in RBP4-induced dyslipidemia Mice. Method : RBP4-induced dyslipidemia mice model established by RBP4 intraperitoneal injection. Model rats are divided in RBP4 One-time exercise group(ROE, 8-weeks RBP4 aerobic exercise group(RAE), and RBP4 control group(RC).Results : Serum RBP4 decreases more in group ROE than group RC(P<0.05).There are no significant differences in serum TG and liver TG between group ROE and group RC(P>0.05). Serum RBP4,TG,and liver TG decreases more in group RAE than group RC and group ROE respectively(P<0.01). Liver ACC1mRNA expression decreases more in group ROE and group RAE than group RC(P<0.01).There are no significant differences in ACC1 protein expression between group RC and group ROE(P>0.05).Liver ACC1 protein expression decreases more in group RAE than group RC and group ROE respectively(P<0.01).Conclusions : RBP4 increases dramatically ACC1mRNA expression in mice liver, and facilitates liver fat synthesis. 8-weeks aerobic exercise could suppress liver fat synthesis, and improve lipid metabolism. The mechanism involves in lowering RBP4, reducing liver ACC1 expression, and TG synthesis after 8-weeks aerobic exercise.

    Keywords

    exerciseRBP4ACC1fat synthesisfat metabolism

  • 脂肪因子视黄醇结合蛋白4(RBP4)能够诱导胰岛素抵抗的产生,还能够调节机体能量平衡,根据机体能量摄取和消耗变化,调节脂肪合成、分解过程,影响脂代谢平衡,是肝脏中脂肪含量的标志物之一 [4]。Xia M等[5]发现:RBP4能够诱导小鼠发生脂代谢紊乱,提高血甘油三酯(TG)水平,机制涉及增加肝脏乙酰辅酶A羧化酶1(ACC1)基因和其他脂肪生成基因表达,促进肝脏脂肪合成和循环TG的释放。ACC是肝脏脂肪合成的主要限速酶,催化脂肪酸(Fatty acid)生成所必需的丙二酰辅酶A(malonyl CoA)的合成过程,促进脂肪酸和TG合成释放,ACC家族中ACC1调节长链脂肪酸合成的能力显著超过ACC2[6-8]。研究还发现:运动能够降低肥胖、2型糖尿病和代谢综合征鼠和患者增高的血清RBP4,改善脂代谢异常,血脂组份TG、总胆固醇(TC)、低密度脂蛋白(LDL-C)水平均显著降低[9-11]

  • 鉴于RBP4能够诱导脂代谢紊乱,升高血TG等指标,机制与增加肝脏ACC1和脂肪生成基因表达、促进肝脏脂肪合成和TG释放入血有关;而运动能够降低RBP4、TG、TC和LDL-C水平,改善脂代谢异常,推测其机制可能与运动抑制RBP4诱导的肝脏ACC1高表达、脂肪合成以及TG释放过程有关。因此,为了探索运动改善RBP4诱导脂代谢紊乱的机制,本文制备RBP4诱导的脂代谢紊乱小鼠模型,给予不同运动处方干预,观察肝脏ACC1表达、TG含量变化以及血RBP4、TG水平,探讨运动改善RBP4诱导的脂代谢紊乱机制,为肥胖、2型糖尿病和代谢综合征等高RBP4血症者的脂代谢异常运动处方治疗提供理论依据和实践指导。

  • 1 材料与方法

  • 1.1 动物造模

  • 实验鼠采用SPF级KM小鼠[SCXK(粤)2013—0020],广州中医药大学(大学城)实验动物中心购买,均为雄性6周龄,体重18—22g,喂养鼠粮为标准鼠粮,自由饮水摄食。

  • KM小鼠随机分为脂代谢紊乱组和对照组。脂代谢紊乱组造模采用RBP4腹腔注射的方法制备脂代谢紊乱模型[6]。具体实施方案:选用重组人RBP4,配置成为80 μg/ml的注射液,分别对造模组KM小鼠进行腹腔注射,每只KM小鼠剂量为1mL,每日注射一次,共持续注射14天。同时给予对照组KM小鼠腹腔注射1mL生理盐水,共注射14天。第14天完成注射后检测KM小鼠空腹血TG(mmol/L)水平,采血部位为眼眶静脉丛。脂代谢紊乱造模组KM小鼠空腹血TG浓度显著高于生理盐水注射对照组(脂代谢紊乱组:1.71±0.03,对照组:1.02±0.01,P <0.01),RBP4诱导的脂代谢紊乱鼠模型制备成功。

  • 1.2 脂代谢紊乱鼠分组及运动方案

  • 对RBP4诱导的脂代谢紊乱模型鼠进行随机分组,设2组运动组和1组安静对照组,即一次性运动组(RBP4One-time exercise group,ROE组)、8周有氧运动组(RBP4aerobic exercise group,RAE组)和安静对照组(RBP4control group,RC组),每组6只。RAE组运动处方参照Ploug T[10]的方案执行:首先进行适应性游泳训练,持续3日,第4日开始执行5次/周的训练方案,每次游泳训练时间为60min,均为无负重。ROE组取材前执行一次相同时间的无负重游泳训练方案。RC组不执行任何运动训练方案。同时还设置没有进行RBP4腹腔注射的正常安静对照组(normal control group,NC组),共6只。

  • 1.3 指标检测

  • RAE组实验鼠于第8周最后一次运动后休息过夜,第二日取材。ROE组亦于第二日执行相同运动处方后,即刻取材,NC组和RC组亦同时取材。所有实验鼠取材前禁食12h,腹腔注射10%水合氯醛,心脏取血,取肝组织备用。

  • ELISA检测小鼠KM血清RBP4水平;酶法测定血TG含量。肝脏TG含量(ummol/g肝组织)检测采用自动生化分析仪,取定量肝脏组织预先进行匀浆,提取组织液中脂质,再进行离心,检测离心后上清液,得出肝脏TG含量[12]。试剂均购买自厦门慧嘉生物公司。

  • RT-PCR法检测ACC1mRNA表达。一步法提取总RNA,内参β-actin上游引物:5 ’-AGATAGACGTGCACAGGAAG-3 ’,下游引物:5 ’-GCTGGCGAACCGCCAGAGCT-3 ’;ACC1上游引物:5 ’CAGGCCGGATGCAGGAGAAG3’,下游引物:5’GAGATGTGCTGGGTCATGTGGAC3’。逆转录依试剂盒说明书进行。凝胶分析系统分析琼脂糖凝胶电泳结果,目标基因与内参基因表达的比值为ACC1mRNA相对表达量。

  • 免疫组化法检测肝脏ACC1蛋白表达。肝组织甲醛固定24h,石蜡切片,脱蜡、水化和抗原恢复,内源性过氧化物酶经过封闭液处理,阻断活性。依次加入一抗、二抗(均采购自厦门慧嘉生物公司),37℃孵育4h,PBS反复冲洗,DBA显色。目标蛋白的平均光密度值(OD)做半定量表达统计,图像分析系统观测单张切片上任意5个视野。

  • 1.4 统计学处理

  • 数据以均数±标准差表示,各组小鼠的数据之间进行单因素方差分析,LSD检验。组间数据差异具有显著统计学意义、非常显著统计学意义分别取P <0.05、P <0.01。数据录入、处理采用SPSS16.0统计软件。

  • 2 结果

  • 游泳运动干预第8周后,RBP4处理的各组小鼠血清RBP4、TG含量,肝脏ACC1mRNA和蛋白表达与NC组相比均显著增加,差异均具有非常显著意义(P <0.01)(表1、表2)。

  • 2.1 一次性运动后血RBP4、血TG、肝脏ACC1表达和肝脏TG变化

  • 与RC组相比,ROE组小鼠血RBP4和肝脏ACC1mRNA表达均显著降低,差异均具有非常显著意义(P <0.01)(表1、图1和表2)。ROE组小鼠血TG、肝脏ACC1蛋白表达、肝脏TG含量与RC组相比,差异均不具有显著性(P >0.05)(表1、图2和表2)。

  • 图1 小鼠肝脏ACC1mRNA表达

  • 2.2 8周有氧运动后血RBP4、血TG、肝脏ACC1表达和肝脏TG变化

  • 与RC组、ROE组相比,RAE组小鼠血RBP4、血TG、肝脏TG含量和肝脏ACC1蛋白表达分别显著降低,差异均具有非常显著意义(P <0.01)(表1、图2和表2)。

  • 表1 小鼠血清RBP4、TG含量变化 ( n=6)

  • 注:与NC组相比,1)P <0.01;与RC组相比,2)P <0.01;与ROE组相比,3)P <0.01。下表同。

  • 图2 实验肝脏ACC1蛋白表达,×400

  • 表2 小鼠肝脏ACC1mRNA和蛋白表达变化 (n=6)

  • 3 讨论

  • 3.1 RBP4与脂代谢紊乱的关系

  • 为了便于研究运动影响RBP4诱导的脂代谢紊乱机制,必须排除其他致脂代谢紊乱的因素,建立RBP4诱导的脂代谢紊乱模型。本研究参照Xia M[5]等的方法建模,采用了高生理剂量的RBP4(80 μg/mL)处理实验鼠。前期研究报道,典型的代谢综合征的RBP4血浆浓度在20—90 μg/mL之间,2型糖尿病和肥胖者的RBP4血浆浓度在40—90 μg/mL之间[9,13,14],因此,本研究中RBP4的浓度具备了诱导脂代谢异常的条件。研究结果显示:与未经过RBP4处理的对照组相比,实验组血TG水平显著增加(P < 0.01),诱导产生了脂代谢紊乱,建模成功,为后续运动干预研究奠定了基础。

  • 以往的研究虽然没有揭示RBP4与脂代谢紊乱之间的因果关系,但是发现了两者间存在的显著相关性,RBP4水平和脂代谢指标升高同时存在于肥胖、2型糖尿病以及代谢综合征者和动物。Xia M[5]等则首次揭示了RBP4与脂代谢紊乱之间的因果关系,通过体外肝细胞培养和活体研究发现,高生理剂量的RBP4能够显著增加C57BL/6J小鼠肝脏脂肪合成调节基因ACC1的表达和活性,促进肝脏脂肪合成和聚集,最终导致肝脏TG含量增加,肝脏VLDL-C向血液分泌量增加,作为血脂组份的TG水平也显著升高。

  • 3.2 运动对RBP4诱导的脂代谢紊乱鼠血TG的影响

  • 本研究中RBP4诱导的脂代谢紊乱鼠血TG显著增加,经过运动干预后,各组实验鼠血TG水平均没有完全恢复到正常生理水平(P >0.05)。与未运动的脂代谢紊乱对照组相比,一次性运动干预也未对脂代谢紊乱鼠的血TG水平产生显著影响(P >0.05)。然而与未运动的脂代谢紊乱对照组相比,8周有氧运动则显著降低了血RBP4和血TG水平(P <0.01),结果与以往的研究一致[15-19]。然而其中的机制尚不十分清楚。

  • 以往大量的研究均报道了运动能够调整脂代谢,降低血TG,改善血脂异常。与肥胖、代谢综合征、酒精等导致脂代谢异常的传统诱因不同,RBP4是一种新近发现的导致脂代谢异常的因素。肝脏和脂肪均是RBP4主要的分泌来源,肝脏又是RBP4发挥作用的靶器官,RBP4分别通过自分泌和内分泌作用在肝脏中发挥脂肪合成的调节功能,RBP4通过过氧化物酶体增殖物激活受体γ辅激活子1b(PGC-1b)途径激活肝脏脂肪生成路径上的关键应答基因ACC1,促进肝脏脂肪合成和VLDL-C分泌增加,血TG水平升高,导致脂代谢紊乱[19-21]

  • 3.3 运动对RBP4诱导的脂代谢紊乱鼠肝脏ACC1表达和脂肪合成的影响

  • 研究显示,运动能够降低ACC的表达,改善脂肪合成,降低血脂水平。16周转轮运动能够显著增加肥胖大鼠肝脏ACC磷酸化水平(非活性蛋白), 减少活性ACC蛋白,降低TG含量[20]。7周的跑台训练能够显著增加肥胖性胰岛素抵抗大鼠骨骼肌ACC磷酸化,抑制骨骼肌的脂肪合成[21]。而本研究中肝脏ACC1基因和蛋白的异常表达则是由RBP4诱导的,与他人研究报道中ACC表达升高的肥胖诱因不同。

  • 本研究观察了肝脏脂肪合成的关键应答基因ACC1表达和肝脏TG情况,来进一步探究运动影响RBP4诱导的脂代谢紊乱机制。研究结果显示,与未经过RBP4处理的正常对照组相比,无论是一次性运动还是8周有氧运动干预均未能完全逆转RBP4诱导的脂代谢紊乱鼠肝脏ACC1表达和脂肪合成的病理改变(表1和表2)。然而与未运动的RBP4诱导的脂代谢紊乱鼠相比,运动还是表现出了一些显著的干预效果,且一次性运动和8周有氧运动呈现了不同的变化特征。

  • 一次性运动仅仅降低RBP4诱导的脂代谢紊乱鼠肝脏ACC1基因表达( P <0.01),未能降低实际发挥脂肪合成促进作用的ACC1蛋白表达(P >0.05),因而肝脏脂肪合成过程并未受到实质性的影响,肝脏TG含量和释放到循环中的TG量也均未发生显著变化(P >0.05);8周有氧运动能够显著降低RBP4诱导的脂代谢紊乱鼠肝脏ACC1基因和蛋白表达(P <0.01),肝脏TG含量和释放到循环中的TG量均显著降低(P <0.01)。提示:8周有氧运动干预后,受到RBP4自分泌和内分泌联合作用的肝脏脂肪合成过程发生了改变,尤其是脂肪合成关键调节物ACC1蛋白表达的减少,是运动改善RBP4诱导的脂代谢紊乱鼠肝脏脂肪合成的主要机制。综合他人有关运动对肥胖ACC表达影响的研究结果,提示长期有氧运动对于多种原因导致的高ACC1性脂肪合成和脂代谢异常均有较理想的干预效果。

  • 4 结语

  • 高RBP4显著增加实验鼠血TG水平,作用方式是增加肝脏ACC1基因、蛋白表达和TG的合成,循环TG释放增加。8周有氧运动能够降低RBP4诱导的脂代谢紊乱鼠血TG水平,改善脂代谢,机制是抑制了肝脏ACC1基因和蛋白表达,降低了TG的合成和含量,循环TG释放减少。

  • 肝脏的脂肪合成过程复杂,涉及众多脂肪合成调节因子。本研究仅通过观察肝脏ACC1和TG含量来反映肝脏的脂肪合成过程,因而尚存在一定的局限性,有待在后续的研究中不断完善。

  • 参考文献

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    • [2] Fitzsimmons R L,Lau P,Muscat G E.Retinoid-related orphan receptor alpha and the regulation of lipid homeostasis[J].J Steroid Biochem Mol Biol,2012,130(3-5):159-168.

    • [3] Romanowska A,Lebensztejn D M,Skiba E,et al.Retinol binding protein-4 as a serum biomarker of intrahepatic lipid content in obese children--preliminary report[J].Acta Biochim Pol,2011,58(1):35-38.

    • [4] Asha G V,Raja G R M,Mahesh M,et al.Male mice are susceptible to high fat diet-induced hyperglycaemia and display increased circulatory retinol binding protein 4(RBP4)levels and its expression in visceral adipose depots[J].Arch Physiol Biochem,2016,122(1):19-26.

    • [5] Xia M,Liu Y,Guo H,et al.Retinol binding protein 4 stimulates hepatic sterol regulatory element-binding protein 1 and increases lipogenesis through the peroxisome proliferator-activated receptor-gamma coactivator 1beta-dependent pathway[J].Hepatology,2013,58(2):564-575.

    • [6] Vavvas D,Apazidis A,Saha A K,et al.Contraction-induced changes in acetyl-CoA carboxylase and 5’-AMP-activated kinase in skeletal muscle[J].J Biol Chem,1997,272(20):13255-13261.

    • [7] Kim K H.Regulation of mammalian acetyl-coenzyme A carboxylase[J].Annu Rev Nutr,1997(17):77-99.

    • [8] Wang Y G,Han X G,Yang Y,et al.Functional differences between AMPK α1 and α2 subunits in osteogenesis,osteoblast-associated induction of osteoclastogenesis,and adipogenesis[J].Sci Rep,2016(6):771-779.

    • [9] Abahusain M A.Retinol-Binding Protein 4 and Insulin Resistance in Lean,Obese,and Diabetic Subjects[J].NEJM,2006,354(24):2552-2563.

    • [10] Soo L,Sung H C,In-Kyong J,et al.Insulin-Sensitizing Effects of Exercise on Adiponectinand Retinol-Binding Protein-4 Concentrations inYoung and Middle-Aged Women[J].J Clin Endocrinol Metab,2008,93(6):2263-2268.

    • [11] Yu Z,Ye X,Wang J,et al.Associations of physical activity with inflammatory factors,adipocytokines,and metabolic syndrome in middle-aged and older chinese people[J].Circulation,2009,119(23):2969-2977.

    • [12] 曾涛,张翠丽.氯仿甲醇匀浆测定肝脏甘油三酯含量[J].卫生研究,2008(5):550-552.

    • [13] Broch M,Vendrell J,Ricart W,et al.Circulating retinol-binding protein-4,insulin sensitivity,insulin secretion,and insulin disposition index in obese and nonobese subjects[J].Diabetes Care,2007,30(7):1802-1806.

    • [14] Cho Y M,Youn B S,Lee H,et al.Plasma retinol-binding protein-4 concentrations are elevated in human subjects with impaired glucose tolerance and type 2 diabetes[J].Am Diabetes Assoc,2006,29(11):2457-2461.

    • [15] Muenzner M,Tuvia N,Deutschmann C,et al.RBP4 and its Membrane Receptor STRA6 Control Adipogenesis by Regulating Cellular Retinoid Homeostasis and RARalpha Activity[J].Mol Cell Biol,2013,39(10):57-64.

    • [16] Berry D C,Noy N.Signaling by vitamin A and retinol-binding protein in regulation of insulin responses and lipid homeostasis[J].Biochim Biophys Acta,2012,1821(1):168-176.

    • [17] Ahima R S,Osei S Y.Adipokines in obesity[J].Front Horm Res,2008,36(1):182-197.

    • [18] 张明军.RBP4对游泳训练大鼠脂肪细胞IR和IRS-1蛋白表达和磷酸化的影响[J].天津体育学院学报,2010,25(1):38-40.

    • [19] Comerford K B,Buchan W,Karakas S E.The Effects of Weight Loss on FABP4 and RBP4 in Obese Women with Metabolic Syndrome[J].Horm Metab Res,2013,11(5):68-75.

    • [20] Rector R S,Thyfault J P,Morris R T,et al.Daily exercise increases hepatic fatty acid oxidation and prevents steatosis in Otsuka Long-Evans Tokushima Fatty rats[J].Am J Physiol Gastrointest Liver Physiol,2008,294(3):619-626.

    • [21] Sriwijitkamol A,Ivy J L,Christ-Roberts C,et al.LKB1-AMPK signaling in muscle from obese insulin-resistant Zucker rats and effects of training[J].Am J Physiol Endocrinol Metab,2006,290(5):925-932.

  • 参考文献

    • [1] Yang Q,Graham T E,Mody N,et al.Serum retinol binding protein4 contributes to insulin resistance in obesity and type 2 diabetes[J].Nature,2005,436(7049):356-362.

    • [2] Fitzsimmons R L,Lau P,Muscat G E.Retinoid-related orphan receptor alpha and the regulation of lipid homeostasis[J].J Steroid Biochem Mol Biol,2012,130(3-5):159-168.

    • [3] Romanowska A,Lebensztejn D M,Skiba E,et al.Retinol binding protein-4 as a serum biomarker of intrahepatic lipid content in obese children--preliminary report[J].Acta Biochim Pol,2011,58(1):35-38.

    • [4] Asha G V,Raja G R M,Mahesh M,et al.Male mice are susceptible to high fat diet-induced hyperglycaemia and display increased circulatory retinol binding protein 4(RBP4)levels and its expression in visceral adipose depots[J].Arch Physiol Biochem,2016,122(1):19-26.

    • [5] Xia M,Liu Y,Guo H,et al.Retinol binding protein 4 stimulates hepatic sterol regulatory element-binding protein 1 and increases lipogenesis through the peroxisome proliferator-activated receptor-gamma coactivator 1beta-dependent pathway[J].Hepatology,2013,58(2):564-575.

    • [6] Vavvas D,Apazidis A,Saha A K,et al.Contraction-induced changes in acetyl-CoA carboxylase and 5’-AMP-activated kinase in skeletal muscle[J].J Biol Chem,1997,272(20):13255-13261.

    • [7] Kim K H.Regulation of mammalian acetyl-coenzyme A carboxylase[J].Annu Rev Nutr,1997(17):77-99.

    • [8] Wang Y G,Han X G,Yang Y,et al.Functional differences between AMPK α1 and α2 subunits in osteogenesis,osteoblast-associated induction of osteoclastogenesis,and adipogenesis[J].Sci Rep,2016(6):771-779.

    • [9] Abahusain M A.Retinol-Binding Protein 4 and Insulin Resistance in Lean,Obese,and Diabetic Subjects[J].NEJM,2006,354(24):2552-2563.

    • [10] Soo L,Sung H C,In-Kyong J,et al.Insulin-Sensitizing Effects of Exercise on Adiponectinand Retinol-Binding Protein-4 Concentrations inYoung and Middle-Aged Women[J].J Clin Endocrinol Metab,2008,93(6):2263-2268.

    • [11] Yu Z,Ye X,Wang J,et al.Associations of physical activity with inflammatory factors,adipocytokines,and metabolic syndrome in middle-aged and older chinese people[J].Circulation,2009,119(23):2969-2977.

    • [12] 曾涛,张翠丽.氯仿甲醇匀浆测定肝脏甘油三酯含量[J].卫生研究,2008(5):550-552.

    • [13] Broch M,Vendrell J,Ricart W,et al.Circulating retinol-binding protein-4,insulin sensitivity,insulin secretion,and insulin disposition index in obese and nonobese subjects[J].Diabetes Care,2007,30(7):1802-1806.

    • [14] Cho Y M,Youn B S,Lee H,et al.Plasma retinol-binding protein-4 concentrations are elevated in human subjects with impaired glucose tolerance and type 2 diabetes[J].Am Diabetes Assoc,2006,29(11):2457-2461.

    • [15] Muenzner M,Tuvia N,Deutschmann C,et al.RBP4 and its Membrane Receptor STRA6 Control Adipogenesis by Regulating Cellular Retinoid Homeostasis and RARalpha Activity[J].Mol Cell Biol,2013,39(10):57-64.

    • [16] Berry D C,Noy N.Signaling by vitamin A and retinol-binding protein in regulation of insulin responses and lipid homeostasis[J].Biochim Biophys Acta,2012,1821(1):168-176.

    • [17] Ahima R S,Osei S Y.Adipokines in obesity[J].Front Horm Res,2008,36(1):182-197.

    • [18] 张明军.RBP4对游泳训练大鼠脂肪细胞IR和IRS-1蛋白表达和磷酸化的影响[J].天津体育学院学报,2010,25(1):38-40.

    • [19] Comerford K B,Buchan W,Karakas S E.The Effects of Weight Loss on FABP4 and RBP4 in Obese Women with Metabolic Syndrome[J].Horm Metab Res,2013,11(5):68-75.

    • [20] Rector R S,Thyfault J P,Morris R T,et al.Daily exercise increases hepatic fatty acid oxidation and prevents steatosis in Otsuka Long-Evans Tokushima Fatty rats[J].Am J Physiol Gastrointest Liver Physiol,2008,294(3):619-626.

    • [21] Sriwijitkamol A,Ivy J L,Christ-Roberts C,et al.LKB1-AMPK signaling in muscle from obese insulin-resistant Zucker rats and effects of training[J].Am J Physiol Endocrinol Metab,2006,290(5):925-932.

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