饲料构成影响大鼠解偶联蛋白-1基因的表达

为探讨不同饲料构成对大鼠褐色脂肪组织解偶联蛋白 1基因表达的影响 ,利用不同的饲料 (包括基础饲料、高蛋白、高脂肪、高能 1与高能 2饲料 )喂养雄性Wistar大鼠 2个月 ,观察不同饲料构成对大鼠体重、脂体比的影响 ,并应用RT PCR、蛋白印迹法测定大鼠褐色脂肪组织UCP1mRNA与蛋白含量。结果高能饲料 1组与高能饲料 2组的体重、脂体比均显著高于基础组、高蛋白组与高脂肪组 (P <0 0 5 ) ,而后三者的体重、脂体比无显著性差异 (P >0 0 5 )。高能饲料 1组与高能饲料 2组UCP1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。说明能量能诱导大鼠褐色脂肪组织UCP1基因表达     

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     

孕期补充二十二碳六烯酸对子代大鼠脂肪代谢及解偶联蛋白2基因表达的影响

目的探讨孕期补充二十二碳六烯酸(DHA)对子代脂肪代谢和解偶联蛋白2基因表达的影响。方法将SD雌鼠按体重随机分成A、B、C三组,孕期分别食用基础膳食(A)、补充低剂量DHA膳食(B)、补充高剂量DHA膳食(C)。所产雄性仔鼠均由A组母鼠哺乳,21d断乳,用基础膳食喂饲至出生后的第8w。将A组仔鼠按体重随机分为正常对照组A1、高脂对照组A2,A1组继续食用基础膳食至实验结束,A2、B、C三组给予高脂膳食喂饲7w,结束实验。在第8w、15w时各组随机选取8只仔鼠处死,观察体重、体脂含量、血脂和白色脂肪UCP2mRNA表达丰度变化。结果各组仔鼠出生体重和出生后第8w体重均无差异(P0.05)。第8w时B、C组仔鼠体脂含量、血清甘油三酯水平显著低于对照组(P0.05);第15w时,A2组体重、体脂含量、甘油三酯均显著高于A1组(P0.05),B、C两组体重和血清甘油三酯水平显著低于A2组(P0.05)。第8w时,B、C两组大鼠白色脂肪组织UCP2mRNA水平均高于A组;15w时,UCP2mRNA水平依次为C组高于B组、A1和A2组,A2组最低。结论孕期适量DHA补充可降低子代大鼠摄取高脂肪膳食时的体重、血清甘油三酯,即降低肥胖发生风险,改善脂肪代谢;其中对子代白色脂肪组织UCP2基因表达的上调作用可能是其潜在机制之一。     

饲料构成影响大鼠解偶联蛋白-2基因的表达

目的 探讨不同饲料构成对大鼠白色脂肪组织解偶联蛋白－2基因表达的影响。方法 利用不同的饲料喂养雄性Wistar大鼠2个月，观察不同饲料构成对大鼠体重、脂体比的影响，并应用RT－PCR方法测定大鼠白色脂肪组织UCP2 mRNA表达水平。结果 高能饲料1组与高能饲料2组的体重、脂体比均显高于基础组、高蛋白组与高脂肪组（P＜0．05），而后三的体重、脂体比无显性差异（P＞0．05）。高能饲料1组与高能饲料2组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。结论 能量能诱导大鼠白色脂肪组织UCP2 mRNA表达，表达的强弱与体内的储存能量多少有关。     

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。     

铁对肥胖大鼠骨骼肌解偶联蛋白基因表达的影响

目的 :　探讨铁对肥胖大鼠骨骼肌中 UCP2、3基因表达的影响。方法 :　利用高脂肪饲料诱导大鼠肥胖模型后 ,观察铁对肥胖大鼠的影响 ,采用放射免疫法检测甲状腺激素水平 ,并应用 RT- PCR方法测定骨骼肌中 UCP2、3m RNA表达水平。结果 :　 1 .适量补铁可改善机体甲状腺素水平 ,而过量补铁对其无影响。2 .缺铁肥胖大鼠 UCP2、3m RNA表达水平明显降低。3.补铁可使肥胖大鼠骨骼肌中 UCP2、3m RNA表达水平增强、体脂含量降低 ,其中以 2 5.51 mg· kg bw-1· d-1剂量铁组 UCP3m RNA表达水平最强 ,约是基础饲料组大鼠的 2倍。高脂饲料诱导的肥胖大鼠骨骼肌中 UCP3 m RNA表达水平较基础饲料组大鼠呈下降趋势。结论 :　适量补铁能改善机体甲状腺素水平 ,促进肥胖大鼠骨骼肌中 UCP2、3 m RNA表达 ,有利于脂肪动员 ,增加能量消耗     

超重及肥胖者与正常成人脂肪组织中解偶联蛋白2基因表达水平的研究

为比较超重及肥胖病人与正常人脂肪组织中解偶联蛋白 2 (UCP 2 )表达水平有无差异 ,探讨UCP 2在肥胖发生中的作用 ,选取 65例做腹部外科手术的病人 ,按体质指数BMI≥ 2 5为超重及肥胖 ,BMI <2 5为体重正常分组。在研究对象进行外科手术的同时采集腹膜内脂肪 ,然后提取其中的RNA ,再通过半定量RT PCR方法对两组研究对象的腹膜内脂肪中UCP 2的mRNA进行检测。结果 :男性超重及肥胖组UCP 2的mR NA相对水平为 0 92± 0 48(UCP 2 β actinamol amol) ,体重正常组为 1 75± 1 2 2 (UCP 2 β actinamol amol) ,两组间有明显差异 (P <0 0 5 ) ;女性超重及肥胖组的UCP 2的mRNA相对水平为 0 93± 0 43 (UCP 2 β actinamol amol) ,体重正常组为 1 48± 0 91(UCP 2 β actinamol amol) ,两组间有显著差异 (P <0 0 5 )。结论 :超重及肥胖病人腹膜内脂肪组织中UCP 2表达水平明显低于体重正常人 ,说明UCP 2在人类肥胖发生中很可能起重要作用     

解偶联蛋白2的功能调控方式

解偶联蛋白（uncoupling protein,UCP）是线粒体内膜的一类线粒体载体蛋白。大量的研究结果显示,UCP功能的异常与多种疾病关系密切。UCP2是UCP的一种重要类型,现综述概括UCP2的主要功能调控方式以及这些调控的生理意义。     

人解偶联蛋白基因多态性与肥胖研究进展

解偶联蛋白（UCP）使线粒体氧化与磷酸化解偶联，从而调节能量代谢，UCP1分布在棕色脂肪，参与人体能量消耗的1%-2%，故不可能在非颤抖性产热中起主要作用，但UCP1的A-G变异与β3肾上腺素能受体Trp64Arg多态性对体重增加可能有协同作用，UCP2和UCP3基因11q13是肥胖和Ⅱ型糖尿病的候选基因，UCP2基因多态性可能通过调节基础代谢率而影响肥胖，UCP3主要分布在骨骼肌，新发现的上游55C-T多态性可能与BMI有关，但编码区基因突变与肥胖的关系有待于进一步研究。     

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.     

Brown adipose tissue: the molecular mechanism of its formation

The function of brown adipose tissue (BAT) is to oxidize fat and to dissipate the energy produced as heat, providing a source of heat to the organism. Preadipocytes are stimulated by expression of the PRDM16 gene to differentiate into BAT cells. The PRDM16 protein is greatly enriched in BAT and causes increased expression of mitochondrial genes and greater density of mitochondria. It increases expression of the uncoupling factor UCP1 and thereby causes a large stimulation of uncoupled respiration with resultant heat production, enhanced by cAMP. Recent evidence strongly supports the idea that the PRDM16 gene determines BAT identity.     

Leptin Improves Parameters of Brown Adipose Tissue Thermogenesis in Lipodystrophic Mice

Lipodystrophy syndromes (LD) are a heterogeneous group of very rare congenital or acquired disorders characterized by a generalized or partial lack of adipose tissue. They are strongly associated with severe metabolic dysfunction due to ectopic fat accumulation in the liver and other organs and the dysregulation of several key adipokines, including leptin. Treatment with leptin or its analogues is therefore sufficient to reverse some of the metabolic symptoms of LD in patients and in mouse models through distinct mechanisms. Brown adipose tissue (BAT) thermogenesis has emerged as an important regulator of systemic metabolism in rodents and in humans, but it is poorly understood how leptin impacts BAT in LD. Here, we show in transgenic C57Bl/6 mice overexpressing sterol regulatory element-binding protein 1c in adipose tissue (Tg (aP2-nSREBP1c)), an established model of congenital LD, that daily subcutaneous administration of 3 mg/kg leptin for 6 to 8 weeks increases body temperature without affecting food intake or body weight. This is associated with increased protein expression of the thermogenic molecule uncoupling protein 1 (UCP1) and the sympathetic nerve marker tyrosine hydroxylase (TH) in BAT. These findings suggest that leptin treatment in LD stimulates BAT thermogenesis through sympathetic nerves, which might contribute to some of its metabolic benefits by providing a healthy reservoir for excess circulating nutrients.     

解偶联蛋白的结构功能及其与肥胖的关系

解偶联蛋白 (UCP)是一种线粒体载体蛋白。在真核细胞线粒体中能量的产生是与氧化磷酸化合成三磷酸腺苷分不开的 ,在棕色脂肪组织中的UCP 1可破坏氧化磷酸化所需的氢质子梯度 ,从而使脂肪细胞中的能量主要以热量形式被消耗。最近在其他一些参与调节呼吸作用和能量代谢的组织中也发现了相似的UCP。因此对UCP及其作用机理的研究 ,对于预防和治疗人类肥胖问题有很重要的意义。     

不同锌营养状况对大鼠铁代谢的影响

目的研究不同锌营养状况对大鼠铁代谢和肝脏铁调节蛋白(IRP)mRNA、铁蛋白(Fn)mRNA及转铁蛋白受体(TfR)mRNA的影响。方法 40只雄性SD大鼠按体重随机分为4组,每组10只,铁和锌正常对照组(ZA组),铁正常锌缺乏组(ZD组),铁和锌正常配饲组(PF组),铁正常锌过量组(ZE组)。喂饲8周后麻醉处死,取大鼠肝脏、脾脏和血清,测定血红蛋白,血清锌、血清铁、血清转铁蛋白受体、血清铁蛋白、肝脏铁和锌含量、脾脏铁和锌含量,并用逆转录-聚合酶链反应(RT-PCR)法检测各组大鼠IRP2 mRNA和肝脏TfR mRNA以及Fn mRNA的表达水平。结果与对照组相比,锌过量使肝脏和脾脏铁含量、血清铁水平显著降低(P<0.05);锌缺乏使肝脏铁含量、血清转铁蛋白受体水平显著增高(P<0.05),同时,血清铁水平显著降低(P<0.05);锌缺乏时肝脏IRP mRNA及TfR mRNA表达显著增强。结论锌缺乏可能通过影响铁吸收、储存、转运来影响体内铁的营养状况。锌缺乏通过改变IRP2表达、IRP-RNA结合活性,在转录后水平改变TfR mRNA和FnmRNA表达,影响铁稳态。     

Effect of dietary protein or amino acids on the rapid change in plasma zinc concentration in rats fed zinc deficient diets

The effects of dietary protein or amino acids on the rapid fall in plasma zinc concentration was studied in rats fed zinc deficient diets. After a 24 hr. fast, young (100 g) rats were given access to a single zinc deficient meal containing various amounts and types of protein or amino acids. Sixteen hours later, plasma zinc levels were determined. EDTA-treated soy protein, egg white and an amino acid mixture, when fed as 20% of the test meal, caused a significant (P<0.05) depression of plasma zinc concentration compared to rats given the zinc deficient meal without protein or amino acids. Plasma zinc could also be significantly lowered (P<0.05) under these conditions by a variety of absorbable chelating agents fed at 2% of the test meal. The effect of dietary protein on plasma zinc concentration could not be attributed to increased urinary zinc excretion in these studies.     

Exogenous Nucleotides Improved the Oxidative Stress and Sirt-1 Protein Level of Brown Adipose Tissue on Senescence-Accelerated Mouse Prone-8 (SAMP8) Mice

Brown adipose tissue (BAT) is of great importance in rodents for maintaining their core temperature via non-shivering thermogenesis in the mitochondria. BAT′s thermogenic function has been shown to decline with age. The activation of adenosine 5′-monophosphate (AMP)-activated protein kinase/sirtuin-1 (AMPK/Sirt-1) is effective in regulating mitochondrial function. Exogenous nucleotides (NTs) are regulatory factors in many biological processes. Nicotinamide mononucleotide (NMN), which is a derivative of NTs, is widely known as a Sirt-1 activator in liver and muscle, but the effect of NMN and NTs on aging BAT has not been studied before. The purpose of this study was to investigate the effect of NTs on aging senescence-accelerated mouse prone-8 (SAMP8) mice. Senescence-accelerated mouse resistant 1 (SAMR1) mice were set as the model control group and NMN was used as the positive control. Male, 3 month old SAMP8 mice were divided into the SAMP8-normal chow (SAMP8-NC), SAMP8-young-normal chow (SAMP8-young-NC), NMN, NTs-free, NTs-low, NTs-medium, and NTs-high groups for long-term feeding. After 9 months of intervention, interscapular BAT was collected for experiments. Compared to the SAMP8-NC, the body weight and BAT mass were significantly improved in the NT-treated aging SAMP8 mice. NT supplementation had effects on oxidative stress in BAT. The concentration of malondialdehyde (MDA) was reduced and that of superoxide dismutase (SOD) increased significantly. Meanwhile, the expression of the brown adipocyte markers uncoupling protein-1 (UCP-1), peroxisome proliferator-activated receptor-γ coactlvator-1α (PGC-1α), and PR domain zinc finger protein 16 (PRDM16) were upregulated. The upregulated proteins may be activated via the Sirt-1 pathway. Thus, NT supplementation may be helpful to improve the thermogenesis of BAT by reducing oxidative stress and activating the Sirt-1 pathway.     

Thermogenesis in cafeteria-fed LA/N-cp (corpulent) rats

The capacity for diet-induced thermogenesis was accessed in groups of 20 week-old lean and corpulent LA/N-cp rats to determine if an impairment in adaptive energy expenditure might be associated with their obese state. Initial body weights of the corpulent rats were twice those of the lean genotype, and the rate of weight gain during cafeteria feeding was four times as rapid as occurred in lean rats. Measurements of resting oxygen consumption were similar in both lean and corpulent rats. Isoproterenol stimulation resulted in a marked increase in oxygen consumption in lean but not in corpulent rats. Acute exposure to a 5°C cold environment resulted in significant decreases in colonic and rectal temperatures in both genotypes but body temperatures recovered more rapidly in lean than in corpulent rats. Cafeteria feeding resulted in an improved cold tolerance only in lean rats. These observations are consistent with an impaired mechanism of diet-induced thermogenesis in the corpulent genotype which may contribute to the development of their obesity.     

The Effects of Chronic Consumption of Lipid-Rich and Delipidated Bovine Dairy Milk on Brown Adipose Tissue Volume in Wild-Type Mice

Brown adipose tissue (BAT) activation is associated with increased energy expenditure by inducing non-shivering thermogenesis. The ingestion of a milk fat globule membrane (MFGM) supplement and a high calorie diet are reported gateways into BAT activation. However, little is known about the effect of the MFGM and high calorie diets on BAT volume. To gain insight into this, mice were maintained on a high-fat (HF) or low-fat (LF) diet in conjunction with either full-cream (FC) or skim bovine dairy milk (BDM). After being maintained on their respective diets for 13 weeks, their body composition, including BAT volume, was measured using X-ray microtomography. A high calorie diet resulted in an increase in the BAT volume and mice consuming an HF diet in conjunction with FC BDM had a significantly greater BAT volume than all the other groups. Conversely, mice consuming an HF diet in addition to skim milk had a lower BAT volume compared to the HF control. The data presented suggest that the consumption of a high calorie diet in conjunction with FC BDM increases the BAT volume in wild-type mice. This study may provide valuable insight into future studies investigating BAT volume and BAT activity in relation to environmental factors, including diet.