低氧运动对营养性肥胖大鼠骨骼肌AMPK-PGC-1α的影响
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摘要
目的:探讨低氧运动对营养性肥胖大鼠骨骼肌AMPK-PGC-1α的影响。方法:构建7周高脂膳食诱导SD大鼠营养性肥胖模型,通过眼眶采血,京都血糖试纸测定血糖(BG),GPO-PAP法测定甘油三酯(TG),COD-PAP法测定总胆固醇(TC),聚乙烯硫酸沉淀法测定低密度脂蛋白(LDL-c);称重,测体长,计算BMI;确认营养性肥胖大鼠模型构建成功。建模后随机分为常氧高脂膳食安静组和运动组(NHQ和NHE组,各10只)、16.3%低氧高脂膳食安静组和运动组(HGQ1和HGE1组,各10只)、13.3%低氧高脂膳食安静组和运动组(HGQ2和HGE2组,各10只),继续高脂饲养,运动组进行8周耐力训练,即20 m/min,40 min/d,5 d/w。末次运动24 h后处死大鼠并采样;Western blotting测定大鼠骨骼细胞中AMPK蛋白、pAMPK蛋白、PGC-1α蛋白表达量。结果:(1)7周高脂膳食可诱导大鼠体重、BMI、BG、TC、LDL-c、TG含量增加(P<0.01或P<0.05)。(2)在大鼠骨骼肌AMPK磷酸化程度方面,HGE1组高于NHQ组(P<0.05),而HGE2组高于NHQ组、NHE组、HGQ1组(P<0.01)。在大鼠骨骼肌PGC-1α蛋白表达方面,HGE2组高于NHQ组(P<0.01),NHE组和HGE1组高于NHQ组(P<0.05);HGE2组高于NHE组(P<0.05);HGE2组和HGE1组均高于HGQ1组(P<0.01或P<0.05)。结论:低氧运动可能通过增强AMPK磷酸化,进而上调PGC-1α蛋白的表达,这可能是低氧运动改善营养性肥胖大鼠骨骼肌脂代谢紊乱的机制之一。
Objective To explore the effect of hypoxia exercise on the protein expression of AMP-activated protein kinase(AMPK) peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α) in the skeletal muscle of the rats with alimentary obesity. Methods The alimentary obesity was induced in Sprague-Dawley rats after 7-week high-fat diet. Then the venous blood was collected to measure the blood glucose(BG),triglyceride(TG),total cholesterol(TC) and low-density lipoprotein(LDL-c) using the kyoto-glucose dipstick,GPO-PAP method,COD-PAP method and polyethylene sulfate precipitation method respectively. The weight and body length of rats both were measured,and the BMI was calculated. After the measuring,rats with successful modelling were randomly divided into a nomoxic group(NHQ),a nomoxic group with endurance exercise(NHE),a 16.3% hypoxia group(HGQ1),a 16.3% hypoxia group with endurance exercise(HGE1),a 13.3% hypoxia group(HGQ2)and a 13.3% hypoxia group with endurance exercise(HGE2),each of 10. All rats continued to receive a high-fat diet,while those of the groups with endurance exercise took a 40-minute treadmill running at the speed of 20 m/min every weekday,lasting 8 weeks. Twenty-four hours after the last exercise,all rats were killed and sampled to detect the protein expression of PGC-1α,pAMPK and AMPK using the Western blotting. Results A 7-week high-fat diet increased the body weight, BMI, BG,CHO, LDL-c and TG of rats significantly. The phosphorylation protein expression of AMPK of the HGE1 group was significantly higher than NHQ group(P<0.05). The phosphorylation protein expression of AMPK of the HGE2 group was significantly higher than the NHQ group,NHE group,and HGQ1 group respectively(P<0.01). The protein expression of PGC-1α of the HGE2,HGE1 and NHE group was significanlty higher than the NHQ group(P<0.01 or P<0.05). The protein expression of PGC-1αof the HGE2 group was significantly higher than the NHE group(P<0.05). The protein expression of PGC-1α of the HGE2 group and HGE1 group was significanlty higher than the HGQ1 group(P<0.01 or P<0.05). Conclusion Hypoxia exercises may up-regulate the protein expression of PGC-1α by enhancing the AMPK phosphorylation,which may be one of the mechanisms that hypoxic exercise improves the lipid metabolism in the skeletal muscle of rats with alimentary obesity.
Objective To explore the effect of hypoxia exercise on the protein expression of AMP-activated protein kinase(AMPK) peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α) in the skeletal muscle of the rats with alimentary obesity. Methods The alimentary obesity was induced in Sprague-Dawley rats after 7-week high-fat diet. Then the venous blood was collected to measure the blood glucose(BG),triglyceride(TG),total cholesterol(TC) and low-density lipoprotein(LDL-c) using the kyoto-glucose dipstick,GPO-PAP method,COD-PAP method and polyethylene sulfate precipitation method respectively. The weight and body length of rats both were measured,and the BMI was calculated. After the measuring,rats with successful modelling were randomly divided into a nomoxic group(NHQ),a nomoxic group with endurance exercise(NHE),a 16.3% hypoxia group(HGQ1),a 16.3% hypoxia group with endurance exercise(HGE1),a 13.3% hypoxia group(HGQ2)and a 13.3% hypoxia group with endurance exercise(HGE2),each of 10. All rats continued to receive a high-fat diet,while those of the groups with endurance exercise took a 40-minute treadmill running at the speed of 20 m/min every weekday,lasting 8 weeks. Twenty-four hours after the last exercise,all rats were killed and sampled to detect the protein expression of PGC-1α,pAMPK and AMPK using the Western blotting. Results A 7-week high-fat diet increased the body weight, BMI, BG,CHO, LDL-c and TG of rats significantly. The phosphorylation protein expression of AMPK of the HGE1 group was significantly higher than NHQ group(P<0.05). The phosphorylation protein expression of AMPK of the HGE2 group was significantly higher than the NHQ group,NHE group,and HGQ1 group respectively(P<0.01). The protein expression of PGC-1α of the HGE2,HGE1 and NHE group was significanlty higher than the NHQ group(P<0.01 or P<0.05). The protein expression of PGC-1αof the HGE2 group was significantly higher than the NHE group(P<0.05). The protein expression of PGC-1α of the HGE2 group and HGE1 group was significanlty higher than the HGQ1 group(P<0.01 or P<0.05). Conclusion Hypoxia exercises may up-regulate the protein expression of PGC-1α by enhancing the AMPK phosphorylation,which may be one of the mechanisms that hypoxic exercise improves the lipid metabolism in the skeletal muscle of rats with alimentary obesity.
引文
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[19]Dong GZ,Lee YI,Jeong JH,et al.Stilbenoids from rheum undulatum protect hepatocytes against oxidative stress through AMPK activation[J].Phytother Res,2015,29(10):1605-1609.
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[21]Friedrichsen M,Mortensen B,Pehm?ller C,et al.Exercise-induced AMPK activity in skeletal muscle:role in glucose uptake and insulin sensitivity[J].Mol Cell Endocrinol,2013,366(2):204-214.
[22]Skeffington KL,Higgins JS,Mahmoud AD,et al.Hypoxia,AMPK activation and uterine artery vasoreactivity[J].J Physiol,2016,594(5):1357-1369.
[23]孙婧瑜,漆正堂,丁树哲.FAT/CD36、AMPK和PGC-1α在运动干预高脂饮食性肥胖中的作用机制[[J].中国运动医学杂志,2013,32(2):174-178.
[24]吴菊花,鞠丽丽,翁锡全,等.低氧刺激影响PGC-1α表达研究进展[J].生命的化学,2016,36(1):81-87.
[25]Greene NP,Fluckey JD,Lambert BS,et al.Regulators of blood lipids and lipoproteins?PPARδand AMPK,induced by exercise,are correlated with lipids and lipoproteins in overweight/obese men and women[J].Am J Physiol Endocrinol Metab,2012,303(10):E1212-E1221.
[26]Nakamura MT,Yudell BE,Loor JJ.Regulation of energy metabolism by long-chain fatty acids[J].Prog Lipid Res,2014,53:124-144.
[27]Shoag J,Arany Z.Regulation of hypoxia-inducible genes by PGC-1 alpha[J].Arterioscler Thromb Vasc Biol,2010,30(4):662-666.
[28]Lee WJ,Kim M,Park HS,et al.AMPK activation increases fatty acid oxidation in skeletal muscle by activating PPARalpha and PGC-1[J].Biochem Biophys Res Commun,2006,340(1):291-295.
[29]J?ger S,Handschin C,St-Pierre J,et al.AMP-activated protein kinase(AMPK)action in skeletal muscle via direct phosphorylation of PGC-1alpha?[J].Proc Natl Acad Sci U S A,2007,104(29):12017-12022.
[30]Zhang Y,Uguccioni G,Ljubicic V,et al.Multiple signaling pathways regulate contractile activity-mediated PGC-1αgene expression and activity in skeletal muscle cells[J].Physiol Rep,2014,2(5):e12008.
[31]Combes A,Dekerle J,Webborn N,et al.Exercise-induced metabolic fluctuations influence AMPK,p38-MAPK and CaMKII phosphorylation in human skeletal muscle[J].Physiol Rep,2015,3(9):e12462.
[32]Chen CY,Tsai YL,Kao CL,et al.Effect of mild intermittent hypoxia on glucose tolerance,muscle morphology and AMPK-PGC-1alpha signaling[J].Chin J Physiol,2010,53(1):62-71.
[33]Chaillou T,Koulmann N,Meunier A,et al.Effect of hypoxia exposure on the recovery of skeletal muscle phenotype during regeneration[J].Mol Cell Biochem,2014,390(1-2):31-40.
[34]陈瑜文,林文弢,邱烈峰,等.间歇低氧运动对肥胖大鼠食欲的影响及其机制分析[J].体育学刊,2011,18(4):133-136.
[2]Jastreboff AM,Kotz CM,Kahan S,et al.Obesity as a disease:the obesity society 2018 position statement[J].Obesity(Silver Spring),2019,27(1):7-9.
[3]Costalat G,Lemaitre F,Tobin B,et al.Intermittent hypoxia revisited:a promising non-pharmaceutical strategy to reduce cardio-metabolic risk factors?[J].Sleep Breath,2018,22(1):267-271.
[4]Kong Z,Zang Y,Hu Y.Normobaric hypoxia training causes more weight loss than normoxia training after a4-week residential camp for obese young adults[J].Sleep Breath,2014,18(3):591-597.
[5]冯连世,张漓,高炳宏,等.不同环境下有氧运动对超重和肥胖青少年体重与体脂含量的影响[J].体育科学,2013,33(11):58-65.
[6]DE Groote E,Britto FA,Bullock L,et al.Hypoxic training improves normoxic glucose tolerance in adolescents with obesity[J].Med Sci Sports Exerc,2018,50(11):2200-2208.
[7]Hardie DG,Ross FA,Hawley SA.AMPK:a nutrient and energy sensor that maintains energy homeostasis[J].Nat Rev Mol Cell Biol,2012,13(4):251-262.
[8]Zhang H,Liu B,Li T,et al.AMPK activation serves a critical role in mitochondria quality control via modulating mitophagy in the heart under chronic hypoxia[J].Int J Mol Med,2018,41(1):69-76.
[9]Hoffman NJ,Parker BL,Chaudhuri R,et al.Global phosphoproteomic analysis of human skeletal muscle reveals a network of exercise-regulated kinases and AMPK substrates[J].Cell Metab,2015,22(5):922-935.
[10]Vargas-Ortiz K,Perez-Vazquez V,Diaz-Cisneros FJ,et al.Aerobic training increases expression levels of SIRT3 and PGC-1αin skeletal muscle of overweight adolescents without change in caloric intake[J].Pediatr Exerc Sci,2015,27(2):177-184.
[11]Rabinovitch RC,Samborska B,Faubert B,et al.AMPK maintains cellular metabolic homeostasis through regulation of mitochondrial reactive oxygen species[J].Cell Rep,2017,21(1):1-9.
[12]Chandler PC,Viana JB,Oswald KD,et al.Feeding response to melanocortin agonist predicts preference for and obesity from a high-fat diet[J].Physiol Behav,2005,85(2):221-230.
[13]Altunkaynak ME,Ozbek E,Altunkaynak BZ,et al.The effects of high-fat diet on the renal structure and morphometric parametric of kidneys in rats[J].J Anat,2008,212(6):845-852.
[14]汤锦花,严海东.营养性肥胖大鼠模型的建立与评价[J].同济大学学报(医学版),2010,31(1):32-34.
[15]钱伯初,史红,吕燕萍.肥胖动物模型的研究进展[J].中国新药杂志,2007,16(15):1159-1162.
[16]Tsch?p M,Heiman ML.Rodent obesity models:an overview[J].Exp Clin Endocrinol Diabetes,2001,109(6):307-319.
[17]张靓,董泽源,马谨,等.跑台运动对高脂饮食诱导的肥胖大鼠骨骼肌肌联素表达的影响[J].中国运动医学杂志,2016,35(6):547-552.
[18]Niederberger E,King TS,Russe OQ,et al.Activation of AMPK and its impact on exercise capacity[J].Sports Med,2015,45(11):1497-1509.
[19]Dong GZ,Lee YI,Jeong JH,et al.Stilbenoids from rheum undulatum protect hepatocytes against oxidative stress through AMPK activation[J].Phytother Res,2015,29(10):1605-1609.
[20]许猛,赵华,曾凡星.急性低氧暴露对大鼠骨骼肌AMPK/TSC2/mTOR信号通路的影响[J].中国运动医学杂志,2015,34(7):699-703.
[21]Friedrichsen M,Mortensen B,Pehm?ller C,et al.Exercise-induced AMPK activity in skeletal muscle:role in glucose uptake and insulin sensitivity[J].Mol Cell Endocrinol,2013,366(2):204-214.
[22]Skeffington KL,Higgins JS,Mahmoud AD,et al.Hypoxia,AMPK activation and uterine artery vasoreactivity[J].J Physiol,2016,594(5):1357-1369.
[23]孙婧瑜,漆正堂,丁树哲.FAT/CD36、AMPK和PGC-1α在运动干预高脂饮食性肥胖中的作用机制[[J].中国运动医学杂志,2013,32(2):174-178.
[24]吴菊花,鞠丽丽,翁锡全,等.低氧刺激影响PGC-1α表达研究进展[J].生命的化学,2016,36(1):81-87.
[25]Greene NP,Fluckey JD,Lambert BS,et al.Regulators of blood lipids and lipoproteins?PPARδand AMPK,induced by exercise,are correlated with lipids and lipoproteins in overweight/obese men and women[J].Am J Physiol Endocrinol Metab,2012,303(10):E1212-E1221.
[26]Nakamura MT,Yudell BE,Loor JJ.Regulation of energy metabolism by long-chain fatty acids[J].Prog Lipid Res,2014,53:124-144.
[27]Shoag J,Arany Z.Regulation of hypoxia-inducible genes by PGC-1 alpha[J].Arterioscler Thromb Vasc Biol,2010,30(4):662-666.
[28]Lee WJ,Kim M,Park HS,et al.AMPK activation increases fatty acid oxidation in skeletal muscle by activating PPARalpha and PGC-1[J].Biochem Biophys Res Commun,2006,340(1):291-295.
[29]J?ger S,Handschin C,St-Pierre J,et al.AMP-activated protein kinase(AMPK)action in skeletal muscle via direct phosphorylation of PGC-1alpha?[J].Proc Natl Acad Sci U S A,2007,104(29):12017-12022.
[30]Zhang Y,Uguccioni G,Ljubicic V,et al.Multiple signaling pathways regulate contractile activity-mediated PGC-1αgene expression and activity in skeletal muscle cells[J].Physiol Rep,2014,2(5):e12008.
[31]Combes A,Dekerle J,Webborn N,et al.Exercise-induced metabolic fluctuations influence AMPK,p38-MAPK and CaMKII phosphorylation in human skeletal muscle[J].Physiol Rep,2015,3(9):e12462.
[32]Chen CY,Tsai YL,Kao CL,et al.Effect of mild intermittent hypoxia on glucose tolerance,muscle morphology and AMPK-PGC-1alpha signaling[J].Chin J Physiol,2010,53(1):62-71.
[33]Chaillou T,Koulmann N,Meunier A,et al.Effect of hypoxia exposure on the recovery of skeletal muscle phenotype during regeneration[J].Mol Cell Biochem,2014,390(1-2):31-40.
[34]陈瑜文,林文弢,邱烈峰,等.间歇低氧运动对肥胖大鼠食欲的影响及其机制分析[J].体育学刊,2011,18(4):133-136.
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