铁对肥胖大鼠解偶联蛋白(UCP2和UCP3)基因表达的影响

为了探讨铁对肥胖大鼠白色脂肪组织中UCP2及骨骼肌中UCP3基因表达的影响 ,应用RT PCR方法测定UCP2、UCP3mRNA表达水平。结果表明 :(1)适量补铁可改善机体甲状腺激素水平 ;(2 ) 5、10、2 0倍铁的高能饲料组肥胖大鼠的脂体比正常铁高能饲料组显著下降 (P <0 0 5 ) ;(3)缺铁使肥胖大鼠UCP2、UC P3mRNA表达水平明显降低 ;(4)补铁可使肥胖大鼠骨骼肌中UCP3mRNA表达水平增强 ,以 5倍 [(2 5 5 1mg (kg·d·BW) ]剂量铁组的UCP3mRNA表达水平最强 ,约是基础饲料组大鼠的 2倍 ;而对高能饲料诱导的白色脂肪组织中的UCP2基因表达增强无影响。结论认为适量补铁能改善机体甲状腺激素水平 ,促进肥胖大鼠骨骼肌中UCP3mRNA表达 ,但不能增加高能诱导的白色脂肪组织中UCP2基因表达     

初断乳大鼠摄入高钙饲料对成年期高脂饲料后解偶联蛋白2基因表达的影响

目的通过对初断乳大鼠的高钙干预及成年后的高脂干预,测定大鼠骨骼肌中解偶联蛋白2(UCP2)mRNA的表达水平,探讨生命早期高钙摄入对成年期肥胖形成的影响。方法初断乳雄性Wistar大鼠120只随机分为正常饲料组和高钙饲料低(2%)、中(2.5%)、高剂量(3%)组。高钙干预4周后检测血脂。随后所有大鼠进行为期3周的基础饲料喂养。于第7周末取血检测血脂。将正常饲料组成年大鼠随机分为正常对照组和肥胖诱导组,肥胖诱导组及3个高钙组均喂以高脂饲料,肥胖诱导8周后处死所有大鼠取血检测血脂并冻存骨骼肌RT-PCR法半定量检测UCP 2基因表达水平。结果高脂干预后3个高钙组的体重增长量均低于肥胖诱导组,低剂量和高剂量组的体重增长量与正常对照组没有差别;高剂量组的血清甘油三酯含量明显低于肥胖诱导组,与正常对照组一致;肥胖诱导组和高剂量组的UCP 2基因表达水平明显低于正常对照组、低剂量和中剂量组;中剂量高钙组的表达水平明显高于正常对照组。结论初断乳大鼠的高钙喂养能够持续发挥作用,使其在成年后的高脂饲料喂养期间,UCP2基因表达增强,血脂紊乱得以改善。     

解偶联蛋白在肥胖抵抗中的作用

目的探讨解偶联蛋白在大鼠抵抗饮食诱导肥胖中的作用.方法将50只健康雄性SD大鼠随机分为对照组和高脂组,分别用基础饲料和高脂饲料喂养13周,然后根据体重和能量摄入量筛选出饮食诱导肥胖抵抗(dietinduced obesity resistance,DIO-R)和饮食诱导肥胖(diet-induced obesity,DIO)组,观察体重的变化;RT-PCR法测定大鼠褐色脂肪、白色脂肪及骨骼肌中解偶联蛋白mRNA水平.结果DIO-R大鼠体重明显低于DIO大鼠(P＜0.05);高脂饲料可增加DIO-R大鼠褐色脂肪解联偶蛋白(UCP)mRNA、白色脂肪UCP2 mRNA及骨骼肌UCP3 mR-NA水平.结论解偶联蛋白表达增加在肥胖抵抗大鼠的能量消耗中起重要作用,是大鼠抵抗肥胖发生的部分原因.     

断乳后不同剂量铁强化膳食对大鼠成年期肥胖诱导后瘦素水平的影响

目的:研究断乳大鼠铁强化膳食对其成年高脂膳食诱导肥胖后血清瘦素水平的影响。方法:将85只初断乳雄性SD大鼠随机分为基础饲料组和高(4倍)、中(3倍)、低(2倍)剂量铁强化组。4周后各组均以基础饲料喂养1周,于第5周末测定大鼠体脂和血清瘦素含量。将基础饲料组16只大鼠随机分为正常对照组和肥胖诱导组,肥胖诱导组和3个铁强化组均喂以高脂饲料。高脂干预8周后处死所有大鼠计算脂/体比,检测血清瘦素含量。结果:高脂干预后,肥胖诱导组体重、体脂含量、瘦素水平均高于其他各组,3个铁强化组瘦素含量高于正常对照组。结论:生命早期适量补铁能够促进大鼠成年期肥胖诱导后的脂肪分解,维持大鼠体重平衡,保证机体瘦素分泌及功能正常。     

UCPs和PPARγ2基因在饮食诱导大鼠肥胖抵抗中的作用

目的探讨白色脂肪组织UCPs和PPARγ2基因在高脂饮食诱导大鼠肥胖抵抗中的作用。方法36只雌性SD大鼠,按体重随机分为高脂实验组和基础对照组,分别给予高脂饲料和基础饲料13周。实验结束时,根据体重将高脂组大鼠分为饮食诱导肥胖(DIO)和饮食诱导肥胖抵抗(DIO-R)大鼠,比较各组大鼠体重、脂肪湿重、脂体比、空腹血糖(FBG)及血脂谱;RT-PCR法测定白色脂肪组织UCP2、UCP3及PPARγ2mRNA的表达水平。结果DIO-R及DIO大鼠脂体比、TC、LDL-C、TG等指标均显著高于对照组相,但DIO-R组体重、脂肪湿重、脂体比、TG显著低于DIO组(P<0.05);DIO-R大鼠UCP2和UCP3mRNA的表达水平高于DIO大鼠和对照组(P<0.01),PPARγ2mRNA的表达水平低于DIO大鼠(P<0.01),高于对照组(P<0.01)。结论高脂饮食诱导大鼠发生肥胖抵抗与白色脂肪组UCP2、UCP3高表达及PPARγ2mRNA表达下降密切相关。     

共轭亚油酸对肥胖大鼠UCP2基因表达的影响

目的 通过研究共轭亚油酸(Conjugated linoleic acid，CLA)对饮食诱导肥胖大鼠解偶联蛋白2(Unconpling protein 2，UCP2)基因表达的影响，探讨CLA降低体重、体脂作用的机制。方法 选用雄性Wistar大鼠，随机分为对照组、高脂组、高脂 CLA组(每100g饲料含CLA分别为0．75，1．50，3．00g)，每组动物10只，观察CLA对肥胖大鼠体重、体脂、血脂水平的影响，并应用RT-PCR的方法检测UCP2 mRNA的表达水平。结果 CLA可降低饮食诱导肥胖大鼠的体重和体脂含量，降低血清甘油三酯、胆固醇、游离脂肪酸水平，并可增加肥胖大鼠脂肪组织UCP2 mRNA的表达水平。结论 CLA可改善肥胖大鼠的脂代谢紊乱，增加UCP2基因的表达，发挥降低体重、体脂的作用。     

饲料构成影响大鼠不同组织中UCP2 mRNA的表达

目的　探讨不同饲料构成对大鼠褐色脂肪组织、白色脂肪组织与骨骼肌解偶联蛋白 - 2基因表达的影响。方法　利用不同的饲料 (包括基础饲料、高蛋白、高脂肪饲料、高能饲料 1与高能饲料 2 )喂养雄性Wistar大鼠 2个月 ,观察不同饲料构成对大鼠体重、脂体比与游离脂肪酸的影响 ,并应用RT PCR方法则定大鼠褐色脂肪组织、白色脂肪组织与骨骼肌UCP2mRNA表达水平。结果　高能饲料 1组与高能饲料 2组的体重、脂体比与游离脂肪酸均显著高于基础组、高蛋白组与高脂肪组 (P <0 0 5 ) ,而后三者的体重、脂体比与游离脂肪酸无显著性差异 (P >0 0 5 )。高能饲料 1与高能饲料 2组白色脂肪组织UCP2基因表达增强 ,而能量相同的基础组、高蛋白组与高脂肪组没有明显差异。各组褐色脂肪组织与骨骼肌UCP2mRNA水平相近。结论　能量能诱导大鼠白色脂肪组织UCP2mRNA表达 ,表达的强弱与体内的储存能量多少有关。褐色脂肪组织与骨骼肌UCP2mRAN表达不受饲料成分的影响。     

饮食诱导肥胖有抵抗性的大鼠解偶联蛋白-2基因的表达

目的　探讨高脂饮食诱导肥胖抵抗大鼠褐色脂肪组织 (BAT)、白色脂肪组织 (WAT)和骨骼肌解偶联蛋白 2 (UCP2 )基因的表达。方法　采用 5 0只健康雄性SD大鼠 ,随机分为对照组和高脂组 ,分别用基础饲料和高脂饲料喂养 13周 ,然后根据体重筛选出DIO R和DIO组观察饮食诱导肥胖抵抗 (DIO R)大鼠体重与能量摄入量的变化 ,应用RT PCR方法测定大鼠褐色脂肪组织、白色脂肪组织和骨骼肌UCP2mRNA表达水平。结果　饮食诱导肥胖 (DIO)大鼠体重与总能量摄入量 (4 89 7± 2 0 5 )g、(3436 3± 14 6 5 )kJl明显高于DIO R大鼠 (4 2 5 1± 2 7 1) g ,(316 93± 94 6 )kJ。白色脂肪组织中 ,DIO R大鼠UCP2mRNA的峰面积为 (35 2± 30 )mm2 ,DIO大鼠UCP2mRNA的峰面积为 (10 1±12 )mm2 ;DIO及DIO R大鼠骨骼肌UCP2mRNA的峰面积分别为 (130± 15 )mm2 、(170± 12 )mm2 ;DIO R大鼠和DIO大鼠褐色脂肪组织UCP2mRNA的峰面积为 (12 4± 14 )mm2 、(14 7± 19)mm2 。结论　DIO R大鼠白色脂肪组织UCP2mRNA表达明显增加 ,提示肥胖抵抗与组织特异增加UCP2的表达相关。     

孕期高中链脂肪膳食对后代UCP3基因的影响

目的:探讨孕期膳食对子代肥胖和肥胖相关基因解偶联蛋白3(UCP3)表达的影响,寻找肥胖预防和治疗的靶标。方法:W istar孕鼠分别食用标准膳食和高中链脂肪膳食,所产雄性子鼠分别为对照组和高中链脂肪酸组(HMCFA),3周断乳后大鼠均食用标准膳食至成年,将对照组的大鼠随机分为两组:一组继续食用标准膳食;另一组为高脂对照组(HFCON),HFCON和HMCFA组的大鼠均高脂膳食诱导肥胖6周。分别在大鼠出生、断乳、成年、高脂诱导肥胖后各处死一批大鼠,取褐色脂肪检测UCP3 mRNA的表达。结果:与孕期标准膳食的子代相比,孕期高中链脂肪膳食可持续降低子代大鼠的体重和肥胖率(P<0.05),同时也可持续升高UCP3 mRNA的表达。结论:孕期高中链脂肪膳食可降低子代成年高脂诱导肥胖的发生;其机制为通过程序性升高子代UCP3基因的表达增加脂肪氧化和热能散失。     

孕期高蛋白膳食对子代大鼠解偶联蛋白和肉毒碱棕榈酰基转移酶的影响

目的探讨孕期膳食对子代肥胖和肥胖相关基因解偶联蛋白（UCP）和肉毒碱棕榈酰基转移酶1（CPT1）表达的影响,寻找肥胖预防和治疗的靶标,寻求合理的孕期膳食。方法将Wistar孕鼠按随机数字表法分为两组,孕期全程分别食用标准膳食（SD）和高蛋白质膳食（HPD）。所产雄性子鼠分别为对照组（CON）和高蛋白质组（HP）,均由CON组的母亲喂养,24d断乳,用SD喂养至成年后,将CON组大鼠按随机数字表法分为两组：一组继续食用SD（CON）;另一组食用高脂膳食（HFD）,为高脂对照组（HFCON）。同时HP组也食用HFD,HFCON和HP组高脂诱导肥胖至实验结束。分期处死大鼠,检测血清甘油三酯（TG）和褐色脂肪中UCP2、UCP3及CPT1mRNA的表达丰度。结果孕期HPD可降低子代断乳前后的体重和高脂诱导肥胖后的体重及肥胖率;断乳时和高脂诱导肥胖后HP组的血清TG分别低于CON和HFCON组;HP组UCP3和CPT1的表达持续高于CON和HFCON组,UCP2的表达在断乳后也持续高于CON和HFCON组;动态观察发现断乳时和高脂诱导肥胖后CPT1的表达均明显升高,高脂诱导肥胖后UCP2、UCP3的表达也明显升高;但在食用SD至成年时CPT1的表达较断乳时略有下降,UCP3的表达与断乳时基本一致。结论孕期适当增加蛋白质摄人可降低子代成年高脂诱导肥胖发生的风险;程序性升高子代UCP2、UCP3和CPT1基因的表达;UCP2、UCP3和CPT1可通过参与脂肪酸氧化调节肥胖的发生。     

膳食钙对高脂膳食大鼠骨骼肌解偶联蛋白3基因表达的影响

为探讨膳食钙对高脂膳食大鼠骨骼肌解偶联蛋白 3 (UCP3 )基因表达的影响 ,将雄性Wistar大鼠随机分成 6组 ,每组 9只 ,分别喂以基础饲料A组 ( 0 5 %钙 )、高脂低钙饲料B组 ( 0 0 8%钙 )、高脂正常钙饲料C组 ( 0 5 %钙 )、高脂高钙饲料D和E组 ( 1%和 1 5 %钙 )和高脂高钙 ( 1 5 %钙 ) +维生素D( 60 0IU % )饲料F组 ,9周后取血测全血血糖、血清瘦素、胰岛素、甲状腺激素 ,应用RT PCR方法测定骨骼肌UCP3mRNA表达水平。结果显示 ,C组体重和体脂含量明显高于A组 (P <0 0 5 ) ,膳食高脂高钙的D、E、F组体重增加的趋势明显降低。C组血糖和胰岛素均有增高趋势 ,C组胰岛素显著高于A、D、E、F组 (P <0 0 5 ) ,但血糖各组无显著性差异 (P >0 0 5 )。与A组相比 ,C组血清瘦素水平显著增高 (P <0 0 5 ) ,D、E、F组血清瘦素有增高趋势 ,但无显著性差异 (P >0 0 5 )。D、E、F组血清游离三碘甲腺原氨酸 (FT3 )明显增高 ,与A、B、C组相比均有极显著性差异 (P <0 0 1)。血清游离四碘甲腺原氨酸 (FT4)各组无显著性差异 (P >0 0 5 )。高脂正常钙的C组骨骼肌UCP3mRNA水平明显低于基础组 ,高脂高钙的D、E、F组UCP3mRNA与C组相比均明显增强。表明膳食钙不但可以改善高脂膳食诱发的体重增加的趋势 ,改善高胰岛素血症 ,还     

钙对高脂膳食大鼠解偶联蛋白基因表达的影响

目的　探讨膳食钙对高脂饮食大鼠白色脂肪组织和骨骼肌解偶联蛋白 2 (uncouplingprotein2 ,UCP2 )基因表达的影响。方法　将雄性Wistar大鼠随机分成 6组 ,每组 9只 ,分别喂以基础饲料A组 (0 5%钙 )、高脂低钙饲料B组 (0 0 8%钙 )、高脂正常钙饲料C组 (0 5%钙 )、高脂高钙饲料D和E组 (1%和 1 5%钙 )和高脂高钙 (1 5%钙 )+维生素D(60 0U % )饲料F组 ,9周后断头取血测血糖、血清胰岛素和瘦素 ,应用RT -PCR方法测定白色脂肪组织和骨路肌UCP2mRNA表达水平。结果　C组体重和体脂含量显著高于其它各组 (P <0 0 1) ,膳食高脂高钙的D、E、F组体重增加的趋势明显降低 ,体重与A组接近 ;C组血糖和胰岛素均有增高趋势 ,C组胰岛素显著高于A、D、E、F组(P <0 0 5) ,但血糖各组无显著性差异 (P >0 0 5)。与A组相比 ,C组血清瘦素水平显著增高 (P <0 0 5) ,D、E、F组血清瘦素有增高趋势 ,但无显著性差异 (P >0 0 5)。高脂高钙的D、E、F组与高脂正常钙的C组相比 ,白色脂肪UCP2mRNA并未增强 ,但骨骼肌UCP2mRNA表达明显增强。高脂低钙的B组白色脂肪UCP2mRNA比C组明显降低。结论　膳食高钙不但可以明显降低体重增加的趋势 ,还可以改善高胰岛素血症 ,促进瘦素分泌和骨骼肌UCP2mRNA的表达 ,有利于肥胖的防治     

Effects of trans-10, cis-12 conjugated linoleic acid on the expression of uncoupling proteins in hamsters fed an atherogenic diet

It is known that conjugated linoleic acid (CLA) feeding decreases body adiposity but the mechanisms involved are not clear. The aim of this study was to analyse whether alterations in uncoupling protein (UCP) expression in white and brown adipose tissues (WAT and BAT, respectively) and in skeletal muscle may be responsible for the effect of trans-10, cis-12 CLA on the size of body fat depots in hamsters. Animals were divided into three groups and fed an atherogenic diet with different amounts of trans-10, cis-12 CLA (0 control, 0.5, or 1 g/100 g diet) for 6 weeks. CLA feeding reduced adipose depot weights, but had no effect on body weight. Leptin mRNA expression decreased in both subcutaneous and perirenal WAT depots, in accordance with lower adiposity, whereas resistin mRNA expression was not changed. Animals fed CLA had lower UCP1 mRNA levels in BAT (both doses of CLA) and in perirenal WAT (the low dose), and lower UCP3 mRNA levels in subcutaneous WAT (the high dose). UCP2 mRNA expression in WAT was not significantly affected by CLA feeding. Animals fed the high dose of CLA showed increased UCP3 and carnitine palmitoyl transferase-I (CPT-I) mRNA expression levels in skeletal muscle. In summary, induction of UCP1 or UCP2 in WAT and BAT is not likely to be responsible for the fat-reduction action of CLA, but the increased expression of UCP3 in skeletal muscle, together with a higher expression of CPT-I, may explain the previously reported effects of dietary CLA in lowering adiposity and increasing fatty acid oxidation by skeletal muscle.     

共轭亚油酸对胰岛素抵抗大鼠葡萄糖运载体4蛋白表达影响的研究

目的通过研究共轭亚油酸（conjugated linoleic acid,CLA）对饮食诱导胰岛素抵抗大鼠葡萄糖运载体4（glucose transporter4,GLUT4）蛋白表达的影响,探讨CLA抗糖尿病作用的机制。方法选用雄性Wistar大鼠,用随机数字表法按体重随机分为对照组、高脂组、高脂＋CLA组（每100g饲料含CLA分别为0．75g、1．50g．3．00g）,每组动物10只,观察CLA对胰岛素抵抗大鼠胰岛素、血糖水平的影响,并应用Western blot方法检测大鼠骨骼肌GLUT4蛋白的表达水平。结果高脂组大鼠血清胰岛素和糖血水平分别为（11．11±2．73）μU／ml、（5．09±0．66）mmol／L,CLA可降低肥胖大鼠的高胰岛素、高糖血症,低、中、高剂量组胰岛素水平分别为（6．99±1．77）μU／ml、（7．36±1．48）μU／ml、（7．85±1．60）μU／ml,血糖水平分别为（4．28±0．72）mmol／L、（4．18±0．55）mmol／L、（4．06±0．63）mmol／L,且高脂组大鼠骨骼肌GLUT4蛋白的表达水平较基础组降低,CLA可增加高脂组大鼠骨骼肌GLUT4蛋白的表达水平。结论CLA可通过增加胰岛素抵抗大鼠骨骼肌GLUT4蛋白的表达水平,改善胰岛素抵抗。     

Long–term dietary high protein intake up–regulates tissue specific gene expression of uncoupling proteins 1 and 2 in rats

Summary Background The consequences of chronic high protein (HP) diets are discussed controversially and are not well understood. Rats adapted to HP exposure show an increased amino acid and fat oxidation and lower feed energy efficiency. We hypothesized that the dietary protein level can affect gene expression of uncoupling protein (UCP) homologues which is suggested to be involved in thermogenesis, substrate oxidation, and energy expenditure. Aim of the study To assess the mRNA expression of UCP homologues in various tissues of rats fed HP diets and to relate UCP gene expression to various parameters of substrate and energy metabolism. To obtain further indications for the possible involvement of UCP in reducing feed energy efficiency under conditions of HP exposure. Methods Adult rats were adapted to casein based diets containing either 13.8% (adequate, AP), 25.7% (medium, MP), or 51.3 % (high, HP) crude protein. Rats were fed for 8 wk and killed in the postabsorptive state. Energy expenditure and mRNA expression were measured using indirect calorimetry and Northern blot analysis, respectively. Pearson correlation coefficients were calculated to determine relationships between UCP mRNA expression and metabolic parameters. Results Hepatic UCP2 mRNA expression was increased by MP and HP diets compared to AP diet. In skeletal muscle UCP2 mRNA expression was lowest under MP conditions. UCP1 mRNA expression in brown adipose tissue (BAT) was significantly increased by HP exposure. The values were inversely associated with feed energy efficiency and positively with energy expenditure and oxygen consumption in the dark period. Skeletal muscle UCP2 and –3 mRNA expression strongly correlated with the plasma free fatty acid concentration, whereas BAT UCP1 and hepatic UCP2 gene expression did not. Conclusions Our results indicate that hepatic UCP2 and BAT UCP1 mRNA expression is related to the level of dietary protein intake. This suggests a role of UCPs in substrate oxidation and in thermogenesis under conditions of HP exposure. Presented in part: The EAAP Symposium on Energy and Protein Metabolism and Nutrition, September 13–18, 2003, Rostock–Warnemuende, Germany.     

Effects of obesity and stable weight reduction on UCP2 and UCP3 gene expression in humans

OBJECTIVES: The molecular determinants of energy expenditure are presently unknown. Recently, two uncoupling protein homologues, UCP2 and UCP3, have been identified. UCP2 is expressed widely, and UCP3 is expressed abundantly in skeletal muscle. Both could be important regulators of energy balance. In this paper, we investigated whether altered UCP2 and UCP3 mRNA levels are associated with obesity or weight reduction. RESEARCH METHODS AND PROCEDURES: UCP2, UCP3 long and short mRNA levels were examined in skeletal muscle and in white adipose tissue of lean, obese, and weight-reduced individuals by RNase protection assay. RESULTS: Expression of UCP2, UCP3S, and UCP3L mRNA in skeletal muscle was similar in lean individuals and in individuals with obesity at stable weight. In contrast, UCP3L and UCP3S mRNAs were decreased by 38% (p<0.0059) and 48% (p<0.0047), respectively, in 20% weight-reduced patients with obesity at stable weight. In contrast, UCP2 mRNA levels were increased by 30% in skeletal muscle of 20% weight-reduced subjects with obesity. In a different set of patients, mostly lean, UCP3L mRNA in skeletal muscle was decreased by 28% (p = 0.0425) after 10% weight reduction at stable weight. Expression of UCP2 mRNA in subcutaneous adipose tissue was similar in lean individuals and in individuals with obesity, and was increased by 58% during active weight loss. DISCUSSION: Stabilization at reduced body weight in humans is associated with a decrease in UCP3 mRNA in muscle. It is possible that reduced UCP3 expression could contribute to decreased energy expenditure in weight-stable, weight-reduced individuals.