鱼胶原蛋白肽对高脂膳食小鼠肝脏脂肪代谢和氧化还原状态的影响
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摘要
目的:研究鱼胶原蛋白肽(fish collagen peptides,FCPs)对高脂膳食(high-fat diet,HFD)小鼠肝脏脂肪代谢和氧化还原状态的影响。方法:54只C57BL/6雄性小鼠按体质量随机分为正常膳食组(CON)、HFD组(HF)和FCPs干预HFD组(PHF)。每周记录各组小鼠体质量,并按体质量把每组小鼠随机均分为两批,分别在第11和22周宰杀,测定采食量、脂肪表观消化率;肝脏中甘油三酯(triglyceride,TG)、总胆固醇和游离脂肪酸(free fatty acid,FFA)含量;肝脏脂代谢相关基因乙酰辅酶A羧化酶1、脂肪酸合成酶、固醇调节元件结合蛋白1c、胆固醇7α-羟化酶(cholesterol 7α-hydroxylase 1,CYP7A1)、过氧化物激活受体α(peroxisome proliferatoractivatedreceptorα,PPARα)和肉毒碱棕榈酰基转移酶1(carnitinepalmity1transferase1,CPT1)的mRNA表达水平,肝脏氧化还原状态相关指标活性氧自由基(reactive oxygen species,ROS)、丙二醛、总抗氧化能力(totalantioxidant capacity,T-AOC)、谷胱甘肽过氧化物酶(glutathion peroxidase,GSH-Px)活力和还原型/氧化型谷胱甘肽的水平。结果:第22周时,与HF组相比,PHF组小鼠的采食量、脂肪和能量摄入显著增加(P<0.05),肝脏的TG、FFA、脂肪空泡和脂肪浸润面积比明显降低(P<0.05),脂肪分解关键基因CYP7A1、PPARα和CPT1的mRNA表达水平显著上调(P<0.05),肝脏的ROS水平显著降低(P<0.05),T-AOC水平和GSH-Px活力显著升高(P<0.05)。结论:质量分数1%FCPs干预可能通过改善HFD小鼠肝脏氧化还原状态,促进肝脏脂肪分解代谢,起到减少小鼠肝脏脂肪蓄积和改善脂代谢。
Objective: To investigate the effects of ?sh collagen peptides(FCPs) on hepatic lipid metabolism and redox status in mice fed with a high-fat diet(HFD). Methods: Male C57 BL/6 mice(4 weeks old) were randomly divided into three groups(18 animals per group) based on body mass: including control normal diet(CON), high-fat diet(HF) and high-fat diet with 1%added FCPs(PHF) groups. Body mass was recorded on a weekly basis. The animals in each group were randomly assigned according to body mass into two groups which were sacri?ced at the end of the 11 th and 22 th week, respectively. Average daily feed intake(ADFI) and apparent fat digestibility(AFD) were determined. Hepatic triglyceride(TG), total cholesterol(TC) and free fatty acid(FFA) were examined. The mRNA expression levels of key regulators of hepatic lipid metabolism such as acety1 CoA-carboxylase 1(ACC-1), fatty acid synthase(FAS), sterol regulatory element-binding protein 1 c(SREBP1 c), cholesterol 7α-hydroxylase 1(CYP7 A1), peroxisome proliferator activated receptor α(PPARα) and carnitine palmity1 transferase 1(CPT1) were analyzed by quantitative real-time polymerase chain reaction(qPCR). The levels of hepatic redox status indicators such as reactive oxygen species(ROS), malondialdehyde(MDA), total antioxidant capacity(T-AOC), glutathione peroxidase(GSH-Px) and ratio of reduced to oxidized glutathione(GSH/GSSG) were determined.Results: After 22 weeks, in comparison to the HF group, the PHF group showed signi?cantly increased levels of ADFI, fat and energy intake(P < 0.05). The concentrations of hepatic TG and FFA, and the ratios of adipose vacuoles and in?ltration area were markedly decreased in the PHF group(P < 0.05). The mRNA expression of CYP7A1, PPARα and CPT1 in liver was signi?cantly up-regulated in the PHF group(P < 0.05). Meanwhile, FCPs improved the redox status due to markedly decreased hepatic ROS(P < 0.05), and significantly increased T-AOC and GSH-Px(P < 0.05). Conclusion: Dietary intervention with 1% FCP can markedly decrease fat accumulation in liver and regulate liver lipid metabolism by improving hepatic redox status and accelerating lipid catabolism in HFD-fed mice.
Objective: To investigate the effects of ?sh collagen peptides(FCPs) on hepatic lipid metabolism and redox status in mice fed with a high-fat diet(HFD). Methods: Male C57 BL/6 mice(4 weeks old) were randomly divided into three groups(18 animals per group) based on body mass: including control normal diet(CON), high-fat diet(HF) and high-fat diet with 1%added FCPs(PHF) groups. Body mass was recorded on a weekly basis. The animals in each group were randomly assigned according to body mass into two groups which were sacri?ced at the end of the 11 th and 22 th week, respectively. Average daily feed intake(ADFI) and apparent fat digestibility(AFD) were determined. Hepatic triglyceride(TG), total cholesterol(TC) and free fatty acid(FFA) were examined. The mRNA expression levels of key regulators of hepatic lipid metabolism such as acety1 CoA-carboxylase 1(ACC-1), fatty acid synthase(FAS), sterol regulatory element-binding protein 1 c(SREBP1 c), cholesterol 7α-hydroxylase 1(CYP7 A1), peroxisome proliferator activated receptor α(PPARα) and carnitine palmity1 transferase 1(CPT1) were analyzed by quantitative real-time polymerase chain reaction(qPCR). The levels of hepatic redox status indicators such as reactive oxygen species(ROS), malondialdehyde(MDA), total antioxidant capacity(T-AOC), glutathione peroxidase(GSH-Px) and ratio of reduced to oxidized glutathione(GSH/GSSG) were determined.Results: After 22 weeks, in comparison to the HF group, the PHF group showed signi?cantly increased levels of ADFI, fat and energy intake(P < 0.05). The concentrations of hepatic TG and FFA, and the ratios of adipose vacuoles and in?ltration area were markedly decreased in the PHF group(P < 0.05). The mRNA expression of CYP7A1, PPARα and CPT1 in liver was signi?cantly up-regulated in the PHF group(P < 0.05). Meanwhile, FCPs improved the redox status due to markedly decreased hepatic ROS(P < 0.05), and significantly increased T-AOC and GSH-Px(P < 0.05). Conclusion: Dietary intervention with 1% FCP can markedly decrease fat accumulation in liver and regulate liver lipid metabolism by improving hepatic redox status and accelerating lipid catabolism in HFD-fed mice.
引文
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[17]丁进锋,苏秀榕,李妍妍,等.海蜇胶原蛋白肽的降血脂及抗氧化作用的研究[J].天然产物研究与开发,2012,24(3):362-365.DOI:10.3969/j.issn.1001-6880.2012.03.019.
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[19]HASEK B E,STEWART L K,HENAGAN T M,et al.Dietary methionine restriction enhances metabolic flexibility and increases uncoupled respiration in both fed and fasted states[J].American Journal of Physiology-Regulatory Integrative and Comparative Physiology,2010,299(3):728-739.DOI:10.1152/ajpregu.00837.2009.
[20]ESFANDIARI N,SHARMA R K,SALEH R A,et al.Utility of the nitroblue tetrazolium reduction test for assessment of reactive oxygen species production by seminal leukocytes and spermatozoa[J].Journal of Andrology,2003,24(6):862-870.DOI:10.1002/j.1939-4640.2003.tb03137.x.
[21]玮屈,陈彦光,吴祖强,等.苦瓜提取物抑制3t3-l1脂肪细胞脂肪沉积研究[J].食品科学,2014,35(5):188-192.DOI:10.7506/spkx1002-6630-201405037.
[22]朱艳萍,杨丽聪,林乐珍,等.咖啡碱和绿原酸对高脂饮食小鼠体质量、脂类沉积及肝脏脂质代谢基因表达的影响[J].食品科学,2017,38(9):162-167.DOI:10.7506/spkx1002-6630-201709026.
[23]LEE G Y,JANG H,LEE J H,et al.Piasy-mediated sumoylation of srebp1c regulates hepatic lipid metabolism upon fasting signaling[J].Molecular and Cellular Biology,2014,34(6):926-938.DOI:10.1128/MCB.01166-13.
[24]丁琳,王丹,薛勇,等.无斑鹞鲼蛋白质对大鼠胆固醇代谢的影响[J].食品科学,2016,37(1):189-193.DOI:10.7506/spkx1002-6630-201601033.
[25]ZARDI E M,NAVARINI L,SAMBATARO G,et al.Hepatic ppars:Their role in liver physiology,fibrosis and treatment[J].Current Medicinal Chemistry,2013,20(27):3370-3396.DOI:10.2174/09298673113209990136.
[26]张建伟.明日叶查耳酮对ⅱ型糖尿病大鼠脂代谢的影响[J].食品科学,2015,36(19):250-254.DOI:10.7506/spkx1002-6630-201519045.
[27]ANUKARAHANONTA T,SHINOZUKA H,FARBER E.Inhibition of protein synthesis in rat liver by d-galactosamine[J].Research Communications in Chemical Pathology&Pharmacology,1973,5(2):481-491.
[28]ZHANG Y,DUAN X,ZHUANG Y.Purification and characterization of novel antioxidant peptides from enzymatic hydrolysates of tilapia(Oreochromis niloticus)skin gelatin[J].Peptides,2012,38(1):13-21.DOI:10.1016/j.peptides.2012.08.014.
[29]江勇,汪少芸,饶平凡.鲨鱼皮明胶水解肽的制备、分离纯化与抗氧化活性研究[J].中国食品学报,2012,12(3):28-33.DOI:10.3969/j.issn.1009-7848.2012.03.005.
[30]陈洁,胡晓赟.蛋白水解物的抗氧化性研究与展望[J].中国食品学报,2011,11(9):111-119.DOI:10.3969/j.issn.1009-7848.2011.09.012.
[31]ALEMAN A,GIMENEZ B,MONTERO P,et al.Antioxidant activity of several marine skin gelatins[J].LWT-Food Science and Technology,2011,44(2):407-413.DOI:10.1016/j.lwt.2010.09.003.
[32]左瑞雅,周小华,杜首英.L-羟脯氨酸-Zn(Ⅱ)的配合机制及其抗氧化性研究[J].生物工程学报,2007,23(4):704-709.
[2]武阳丰,马冠生,胡永华,等.中国居民的超重和肥胖流行现状[J].中华预防医学杂志,2005(5):22-26.DOI:10.3760/j:issn:0253-9624.2005.05.006.
[3]NG M,FLEMING T,ROBINSON M,et al.Global,regional,and national prevalence of overweight and obesity in children and adults during 1980-2013:a systematic analysis for the global burden of disease study 2013[J].Lancet,2014,384:766-781.DOI:10.1016/S0140-6736(14)60460-8.
[4]MARTIN K A,MANI M V,MANI A.New targets to treat obesity and the metabolic syndrome[J].European Journal of Pharmacology,2015,763:64-74.DOI:10.1016/j.ejphar.2015.03.093.
[5]LOMBA A,MILAGRO F I,GARCIA-DIAZ D F,et al.Obesity induced by a pair-fed high fat sucrose diet:methylation and expression pattern of genes related to energy homeostasis[J].Lipids in Health and Disease,2010,9:60.DOI:10.1186/1476-511X-9-60.
[6]GREGORIO B M,DE SOUZA D B,DE MORAIS NASCIMENTO FA,et al.The potential role of antioxidants in metabolic syndrome[J].Current Pharmaceutical Design,2016,22(7):859-869.
[7]MANGGE H,SUMMERS K,ALMER G,et al.Antioxidant food supplements and obesity-related inflammation[J].Current Medicinal Chemistry,2013,20(18):2330-2337.DOI:10.2174/0929867311320180004.
[8]胡济美,李倬林,岳玉兰,等.刺玫籽油及原花青素降血脂作用[J].食品科学,2017,38(13):213-218.DOI:10.7506/spkx1002-6630-201713035.
[9]李龙囡,王艳艳,尹彩娜,等.硫辛酸对高脂日粮小鼠脂代谢紊乱及氧化应激的调节作用[J].食品与生物技术学报,2013(6):608-614.DOI:10.3969/j.issn.1673-1689.2013.06.009.
[10]BHUTANI G,GUPTA M C.Emerging therapies for the treatment of osteoporosis[J].Journal of Mid-Life Health,2013,4(3):147-152.DOI:10.4103/0976-7800.118991.
[11]陈建康,包建强.酶解法制备草鱼皮蛋白水解物增殖嗜热链球菌[J].食品科学,2016,37(5):144-148.DOI:10.7506/spkx1002-6630-201605026.
[12]郭玉华,刘扬瑞,李钰金.鱼类胶原蛋白及胶原活性多肽的研究进展[J].中国食品添加剂,2010(3):175-179.DOI:10.3969/j.issn.1006-2513.2010.03.033.
[13]周先艳,樊建,唐远龙,等.罗非鱼皮胶原蛋白水解产物的体外抗氧化活性和体内抗衰老作用[J].食品科学,2016,37(15):221-226.DOI:10.7506/spkx1002-6630-201615037.
[14]朱琳玲,白静,周青青,等.骨胶原多肽对小鼠抗氧化能力和皮肤、骨骼胶原蛋白mRNA表达的影响[EB/OL].北京:中国科技论文在线.(2017-04-06)[2012-04-16].http://www.paper.edu.cn/releasepaper/content/201204-213.
[15]蔡路昀,马帅,曹爱玲,等.不同部位鲽鱼皮酸溶性胶原蛋白的提取及其特性[J].食品科学,2017,38(11):52-58.DOI:10.7506/spkx1002-6630-201711009.
[16]李亚欣,施用晖,王洁昀,等.胶原蛋白肽对高脂日粮小鼠抗氧化能力和血脂代谢的影响[J].天然产物研究与开发,2011,25(1):54-58;68.DOI:10.3969/j.issn.1001-6880.2011.01.012.
[17]丁进锋,苏秀榕,李妍妍,等.海蜇胶原蛋白肽的降血脂及抗氧化作用的研究[J].天然产物研究与开发,2012,24(3):362-365.DOI:10.3969/j.issn.1001-6880.2012.03.019.
[18]PONZIANI F R,PECERE S,GASBARRINI A,et al.Physiology and pathophysiology of liver lipid metabolism[J].Expert Review of Gastroenterology&Hepatology,2015,9(8):1055-1067.DOI:10.1586/17474124.2015.1056156.
[19]HASEK B E,STEWART L K,HENAGAN T M,et al.Dietary methionine restriction enhances metabolic flexibility and increases uncoupled respiration in both fed and fasted states[J].American Journal of Physiology-Regulatory Integrative and Comparative Physiology,2010,299(3):728-739.DOI:10.1152/ajpregu.00837.2009.
[20]ESFANDIARI N,SHARMA R K,SALEH R A,et al.Utility of the nitroblue tetrazolium reduction test for assessment of reactive oxygen species production by seminal leukocytes and spermatozoa[J].Journal of Andrology,2003,24(6):862-870.DOI:10.1002/j.1939-4640.2003.tb03137.x.
[21]玮屈,陈彦光,吴祖强,等.苦瓜提取物抑制3t3-l1脂肪细胞脂肪沉积研究[J].食品科学,2014,35(5):188-192.DOI:10.7506/spkx1002-6630-201405037.
[22]朱艳萍,杨丽聪,林乐珍,等.咖啡碱和绿原酸对高脂饮食小鼠体质量、脂类沉积及肝脏脂质代谢基因表达的影响[J].食品科学,2017,38(9):162-167.DOI:10.7506/spkx1002-6630-201709026.
[23]LEE G Y,JANG H,LEE J H,et al.Piasy-mediated sumoylation of srebp1c regulates hepatic lipid metabolism upon fasting signaling[J].Molecular and Cellular Biology,2014,34(6):926-938.DOI:10.1128/MCB.01166-13.
[24]丁琳,王丹,薛勇,等.无斑鹞鲼蛋白质对大鼠胆固醇代谢的影响[J].食品科学,2016,37(1):189-193.DOI:10.7506/spkx1002-6630-201601033.
[25]ZARDI E M,NAVARINI L,SAMBATARO G,et al.Hepatic ppars:Their role in liver physiology,fibrosis and treatment[J].Current Medicinal Chemistry,2013,20(27):3370-3396.DOI:10.2174/09298673113209990136.
[26]张建伟.明日叶查耳酮对ⅱ型糖尿病大鼠脂代谢的影响[J].食品科学,2015,36(19):250-254.DOI:10.7506/spkx1002-6630-201519045.
[27]ANUKARAHANONTA T,SHINOZUKA H,FARBER E.Inhibition of protein synthesis in rat liver by d-galactosamine[J].Research Communications in Chemical Pathology&Pharmacology,1973,5(2):481-491.
[28]ZHANG Y,DUAN X,ZHUANG Y.Purification and characterization of novel antioxidant peptides from enzymatic hydrolysates of tilapia(Oreochromis niloticus)skin gelatin[J].Peptides,2012,38(1):13-21.DOI:10.1016/j.peptides.2012.08.014.
[29]江勇,汪少芸,饶平凡.鲨鱼皮明胶水解肽的制备、分离纯化与抗氧化活性研究[J].中国食品学报,2012,12(3):28-33.DOI:10.3969/j.issn.1009-7848.2012.03.005.
[30]陈洁,胡晓赟.蛋白水解物的抗氧化性研究与展望[J].中国食品学报,2011,11(9):111-119.DOI:10.3969/j.issn.1009-7848.2011.09.012.
[31]ALEMAN A,GIMENEZ B,MONTERO P,et al.Antioxidant activity of several marine skin gelatins[J].LWT-Food Science and Technology,2011,44(2):407-413.DOI:10.1016/j.lwt.2010.09.003.
[32]左瑞雅,周小华,杜首英.L-羟脯氨酸-Zn(Ⅱ)的配合机制及其抗氧化性研究[J].生物工程学报,2007,23(4):704-709.