低氧运动对胰岛素抵抗大鼠脂肪组织缺氧状况的影响
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摘要
目的:探讨缺氧对胰岛素抵抗大鼠脂肪组织的影响,为运动治疗肥胖和胰岛素抵抗提供新的理论依据。方法:通过8周的高脂饮食筛选出符合建模标准的大鼠,建立胰岛素抵抗大鼠模型。将24只成模大鼠随机分为4组,每组6只:常氧安静组(NC)、常氧运动组(NE)、低氧安静组(HC)和低氧运动组(HE)。其中,NE和HE组大鼠采用水平动物跑台进行运动训练,HC和HE组大鼠施以13.7%氧浓度干预,实验期间隔天称量大鼠体重。实验结束后处死大鼠并剥离其肾周及睾周脂肪,称量重量。取睾周脂肪制作冰冻切片,行HE染色观察脂肪细胞直径的变化;Western Blot检测脂肪组织中HIF-1α和Glut-1的蛋白表达。结果:4周低氧运动能够显著降低大鼠体重及增长幅度(P<0.05)。NE和HE组大鼠肾周及睾周脂肪总含量显著低于其他组(P<0.05),两组间无明显差异;各组大鼠的脂肪组织直径均显著低于对照组(P<0.05)。运动及低氧能够显著降低脂肪组织中HIF-1α的蛋白表达(P<0.05),对Glut-1的蛋白表达无明显影响。结论:从减缓体重增加幅度及脂肪含量角度来看,低氧运动和常氧运动减体重的效果优于单纯低氧暴露。低氧和运动都能显著改善脂肪组织的缺氧状况,但对糖代谢无明显影响。常氧运动更有利于改善胰岛素抵抗个体中脂肪组织的缺氧状况。
Objective: To explore the changes of a series of indexes of adipose tissue in hypoxic exercise in a high-fat diet(HFD) induced insulin resistance rats model, and preliminarily investigate the effects of hypoxia on adipose tissue in rats with insulin resistance, so as to provide a new theoretical basis for exercise treatment of obesity and insulin resistance. Methods: The rats were screened by a HFD for 8 weeks and a model of insulin resistance was established. The 24 rats were randomly divided into 4 groups: control group(NC, n=6), normoxic exercise group(NE), hypoxic quiet group(HC, n=6) and hypoxic exercise group(HE, n=6). The rats in NE and HE were trained by the horizontal animal running platform, and the rats in HC and HE were treated with 13.7% oxygen concentration, and the rats were weighted in the next day during the test period. After the experiment, the rats were killed. Their perirenal and epididymal adipose tissue were stripped and weighted. The changes of adipocyte diameter were observed by HE staining. Western blot detected the protein expression of HIF-1α and Glut-1 in adipose tissue. Results: 4-week hypoxic and exercise can significantly reduce the weight and increase of rats(P<0.05). The total fat content of the rats in exercise groups was significantly lower than that of other groups(P<0.05), while showed no significant difference between the two exercise groups(P>0.05). The adipocyte diameter in each group was significantly lower than that in the control group(P<0.05). Exercise and hypoxia can significantly reduce the expression of HIF-1α in adipose tissue(P<0.05), which has no significant effect on the protein expression of Glut-1(P>0.05). Conclusion: From the perspective of slowing down the body weight gain and fat content, the effect of weight loss in normoxic exercise and hypoxic exercise are better than that of pure hypoxic exposure. Both hypoxia and exercise can significantly improve the status of anoxia in adipose tissue, but have no obvious effect on glucose metabolism. Normoxic exercise is more beneficial to improve the anoxia of adipose tissue in individuals with insulin resistance.
Objective: To explore the changes of a series of indexes of adipose tissue in hypoxic exercise in a high-fat diet(HFD) induced insulin resistance rats model, and preliminarily investigate the effects of hypoxia on adipose tissue in rats with insulin resistance, so as to provide a new theoretical basis for exercise treatment of obesity and insulin resistance. Methods: The rats were screened by a HFD for 8 weeks and a model of insulin resistance was established. The 24 rats were randomly divided into 4 groups: control group(NC, n=6), normoxic exercise group(NE), hypoxic quiet group(HC, n=6) and hypoxic exercise group(HE, n=6). The rats in NE and HE were trained by the horizontal animal running platform, and the rats in HC and HE were treated with 13.7% oxygen concentration, and the rats were weighted in the next day during the test period. After the experiment, the rats were killed. Their perirenal and epididymal adipose tissue were stripped and weighted. The changes of adipocyte diameter were observed by HE staining. Western blot detected the protein expression of HIF-1α and Glut-1 in adipose tissue. Results: 4-week hypoxic and exercise can significantly reduce the weight and increase of rats(P<0.05). The total fat content of the rats in exercise groups was significantly lower than that of other groups(P<0.05), while showed no significant difference between the two exercise groups(P>0.05). The adipocyte diameter in each group was significantly lower than that in the control group(P<0.05). Exercise and hypoxia can significantly reduce the expression of HIF-1α in adipose tissue(P<0.05), which has no significant effect on the protein expression of Glut-1(P>0.05). Conclusion: From the perspective of slowing down the body weight gain and fat content, the effect of weight loss in normoxic exercise and hypoxic exercise are better than that of pure hypoxic exposure. Both hypoxia and exercise can significantly improve the status of anoxia in adipose tissue, but have no obvious effect on glucose metabolism. Normoxic exercise is more beneficial to improve the anoxia of adipose tissue in individuals with insulin resistance.
引文
[1] EDITORIAL.Obesity:a growing threat to health in China[J].The Lancet,2014,384(9945):716.
[2] YEJ.Emerging role of adipose tissue hypoxia in obesity and insulin resistance[J].Int Obes (Lond),2009,33(1):54-66.
[3] ALEXOPOULOS N,KATRITSIS D,RAGGI P.Visceral adipose tissue as a source of inflammation and promoter of atherosclerosis[J].Atherosclerosis,2014,233(1):104-112.
[4] ITO T,NOGUCHI Y,SATOH S,et al.Expression of facilitative glucose transporter isoforms in lung carcinomas:Its relation to histologic type,differentiation grade,and tumor stage[J].Mod Pathol,1998,11(5):437-443.
[5] PAUL T,BOHAN W,STUART W I.Hypoxia in adipose tissue:a basis for the dysregulation of tissue function in obesity?[J].Br J Nutr,2008,100(2):227-235.
[6] 李光,李昶,王玮,等.间歇低氧小鼠胰岛素抵抗增加及其适应性的研究[J].中国现代医学杂志,2014,24(8):17-21.
[7] KOLESNYK I U,IUM O,SEREDENKO M M,et al.The effect of intermittent hypoxic training on pancreatic endocrine function in animals with diabetes mellitus [J].FiziolZh,1994,40(5-6):87-95.
[8] 张荷,周越,张一民,等.低氧运动对肥胖大鼠胰岛素抵抗及血脂代谢的影响[J].北京体育大学学报,2016,39(9):44-49.
[9] 刘欣秋,雷鸣,赵安飞,等.实验性NIDDM模型胰岛素抵抗的评估[J].中国误诊学杂志,2001,1(4):492-494.
[10] 李光伟,潘孝仁,STEPHEN L,等.检测人群胰岛素敏感性的一项新指数[J].中华内科杂志,1993,32(10):656-660.
[11] SUN S,JI Y,KERSTEN S,et al.Mechanisms of inflammatory responses in obese adipose tissue [J].Annu Rev Nutr,2012,32(1):261-286.
[12] RAUSCH M E,WEISBERG S,VARDHANA P,et al.Obesity in C57L/6J mice in characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration [J].Int J Obes (Lond),2008,32(3):451-463.
[13] LEE YS,KIM J,OSBORNE O,et al.Increased adipocyte O-2 consumption triggers HIF-1α,causing inflammation and insulin resistance in obesity[J].Cell,2014,157(6):1339-1352.
[14] KITADE H,SAWAMOTO K,NAGASHIMADA M,et al.CCR5 plays a critical role in obesity-induced adipose inflammation and insulin resistance by regulating both macrophage recruitment and M1/M2 status [J].Diabetes,2012,61(7):1680-1690.
[15] CAI X,HUANG Y,ZHANG X,et al.Cloning,characterization,hypoxia and heat shock response of hypoxia inducible factor-1 (HIF-1) from the small abalone Haliotisdiversicolor [J].Gene,2014,534(2):256-264.
[16] JOOST H G,THORENS B.The extended GLUT-family of sugar/polyol transport facilitators:nomenclature,sequence characteristics,and potential function of its novel members [J].Mol Membr Biol,2001,18(4):247-256.
[17] PARK H S,KIM J H,SUN B K,et al.Hypoxia induces glucose uptake and metabolism of adipose-derived stem cells [J].Mol Med Rep,2016,14(5):4706-4714.
[18] 黄徐根,冯连世,徐建方,等.低氧训练过程中大鼠体重及能量代谢的变化[J].体育科学,2007,27(10):61-68.
[19] TAKATA K,KASAHARA T,KASAHARA M,et al.Erythrocyte/HepG2-type glucose transporter is concentrated in cells of blood-tissue barrier [J].BiochemBiophys Res Commun,1990,173(1):67-73.
[20] 杨贵明,范锦勤,翁锡全.间歇低氧结合运动对IR大鼠血清及股四头肌抗氧化能力的影响[J].上海体育学院学报,2017,41(1):38-42.
[21] 张坦,孙易,丁树哲.线粒体自噬在运动改善胰岛素抵抗中的作用[J].上海体育学院学报,2017,41(1):50-54.
[2] YEJ.Emerging role of adipose tissue hypoxia in obesity and insulin resistance[J].Int Obes (Lond),2009,33(1):54-66.
[3] ALEXOPOULOS N,KATRITSIS D,RAGGI P.Visceral adipose tissue as a source of inflammation and promoter of atherosclerosis[J].Atherosclerosis,2014,233(1):104-112.
[4] ITO T,NOGUCHI Y,SATOH S,et al.Expression of facilitative glucose transporter isoforms in lung carcinomas:Its relation to histologic type,differentiation grade,and tumor stage[J].Mod Pathol,1998,11(5):437-443.
[5] PAUL T,BOHAN W,STUART W I.Hypoxia in adipose tissue:a basis for the dysregulation of tissue function in obesity?[J].Br J Nutr,2008,100(2):227-235.
[6] 李光,李昶,王玮,等.间歇低氧小鼠胰岛素抵抗增加及其适应性的研究[J].中国现代医学杂志,2014,24(8):17-21.
[7] KOLESNYK I U,IUM O,SEREDENKO M M,et al.The effect of intermittent hypoxic training on pancreatic endocrine function in animals with diabetes mellitus [J].FiziolZh,1994,40(5-6):87-95.
[8] 张荷,周越,张一民,等.低氧运动对肥胖大鼠胰岛素抵抗及血脂代谢的影响[J].北京体育大学学报,2016,39(9):44-49.
[9] 刘欣秋,雷鸣,赵安飞,等.实验性NIDDM模型胰岛素抵抗的评估[J].中国误诊学杂志,2001,1(4):492-494.
[10] 李光伟,潘孝仁,STEPHEN L,等.检测人群胰岛素敏感性的一项新指数[J].中华内科杂志,1993,32(10):656-660.
[11] SUN S,JI Y,KERSTEN S,et al.Mechanisms of inflammatory responses in obese adipose tissue [J].Annu Rev Nutr,2012,32(1):261-286.
[12] RAUSCH M E,WEISBERG S,VARDHANA P,et al.Obesity in C57L/6J mice in characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration [J].Int J Obes (Lond),2008,32(3):451-463.
[13] LEE YS,KIM J,OSBORNE O,et al.Increased adipocyte O-2 consumption triggers HIF-1α,causing inflammation and insulin resistance in obesity[J].Cell,2014,157(6):1339-1352.
[14] KITADE H,SAWAMOTO K,NAGASHIMADA M,et al.CCR5 plays a critical role in obesity-induced adipose inflammation and insulin resistance by regulating both macrophage recruitment and M1/M2 status [J].Diabetes,2012,61(7):1680-1690.
[15] CAI X,HUANG Y,ZHANG X,et al.Cloning,characterization,hypoxia and heat shock response of hypoxia inducible factor-1 (HIF-1) from the small abalone Haliotisdiversicolor [J].Gene,2014,534(2):256-264.
[16] JOOST H G,THORENS B.The extended GLUT-family of sugar/polyol transport facilitators:nomenclature,sequence characteristics,and potential function of its novel members [J].Mol Membr Biol,2001,18(4):247-256.
[17] PARK H S,KIM J H,SUN B K,et al.Hypoxia induces glucose uptake and metabolism of adipose-derived stem cells [J].Mol Med Rep,2016,14(5):4706-4714.
[18] 黄徐根,冯连世,徐建方,等.低氧训练过程中大鼠体重及能量代谢的变化[J].体育科学,2007,27(10):61-68.
[19] TAKATA K,KASAHARA T,KASAHARA M,et al.Erythrocyte/HepG2-type glucose transporter is concentrated in cells of blood-tissue barrier [J].BiochemBiophys Res Commun,1990,173(1):67-73.
[20] 杨贵明,范锦勤,翁锡全.间歇低氧结合运动对IR大鼠血清及股四头肌抗氧化能力的影响[J].上海体育学院学报,2017,41(1):38-42.
[21] 张坦,孙易,丁树哲.线粒体自噬在运动改善胰岛素抵抗中的作用[J].上海体育学院学报,2017,41(1):50-54.