甘露糖-6-磷酸对脂肪细胞分化的影响及其分子机制初探

目的 探讨甘露糖-6-磷酸(M6P)对脂肪细胞分化的影响及其分子机制.方法 油红O染色、测定TG及甘油含量观察M6P对3T3-L1前脂肪细胞株脂肪细胞分化进程的影响.激光共聚焦显微镜下观察组织蛋白酶K(CTSK)酶活性变化,四甲基偶氮唑盐比色法(MTT)检测前脂肪细胞增殖情况,同时RT-PCR检测M6P受体(M6PR)转录表达.结果 经不同浓度M6P干预后,油红O染色逐渐变浅,当M6P 10 mmol/L时细胞完全不被染色.同时TG合成及甘油含量明显下降,有剂量依赖关系,浓度分别为5 mmol/L和8 mmol/L时即与对照组差异有统计学意义(P＜0.05).脂肪细胞分化进程中的不同时间点均可检测到M6PR mRNA表达.加入M6P后CTSK酶活性呈剂量依赖性被抑制,10 mmol/L时,CTSK酶活性被完全抑制.MTT显示M6P加入后细胞增殖,10 mmol/L的M6PA值达到0.057±0.091,与对照组相比增加了62.9%(P＜0.05).结论 在3T3-L1前脂肪细胞中同样有M6PR表达,M6P可能通过竞争结合M6PR抑制CTSK酶活性,从而影响脂肪细胞分化进程.     

JNK介导TNF-α和H2O2引起的脂肪细胞胰岛素抵抗

目的：探讨c-Jun氨基端激酶（JNK）对肿瘤坏死因子-α（TNF-α）和H2O2引起的脂肪细胞胰岛素抵抗的介导作用。方法：3T3-L1前脂肪细胞分化成熟后,向培养基中添加1 nmol/L TNF-α或50 U/L 葡萄糖氧化酶（GO）产生低浓度H2O2诱导建立胰岛素抵抗脂肪细胞模型,观察JNK1 siRNA转染或JNK特异性抑制剂SP600125（20 μmol/L）预处理对脂肪细胞葡萄糖摄取能力的影响。结果：经过TNF-α或H2O2处理12 h,脂肪细胞在胰岛素刺激后对葡萄糖的摄取能力分别降至对照细胞的46%和52%（P＜0.01）,该抑制效应可被siRNA转染引起的JNK1蛋白沉默所阻断;SP600125预处理可以将TNF-α或H2O2处理脂肪细胞的葡萄糖摄取能力分别提高约66%和62%（P＜0.01）。结论：JNK在TNF-α和H2O2诱导的脂肪细胞胰岛素抵抗中发挥介导作用,抑制JNK过度活化有望成为治疗胰岛素抵抗的新靶点。     

Immunologic changes in obesity

A growing body of literature suggests multifaceted alterations to the immune function in obese patients compared with a lean cohort. Although treatment in the intensive care unit has an associated risk of infectious complications, which, if any, of these immunologic alterations are causal is unclear. Obesity clearly causes abundant alterations to the immune system. Overall, the aggregate effect seems to be chronic activation of inflammatory mediators.     

Single nucleotide polymorphisms of the resistin (RSTN) gene

Type 2 diabetes mellitus is a complex phenotype that is frequently associated with central obesity and insulin resistance. Recently, a protein named resistin, encoded by RSTN (OMIM #605565), was identified in adipose tissue. Serum resistin was elevated in obese and diabetic mice, and administration of resistin to normal mice was found to interfere with glucose tolerance and insulin action. Because of these functions, resistin is a candidate gene for diabetes and obesity. Through the use of DNA sequencing, we thus developed amplification primers for rapid screening of the RSTN gene that encodes resistin. No putative mutations were found, but two noncoding single-nucleotide polymorphisms (SNPs) were identified, and these were found to vary in frequency across various ethnic groups. The identification of amplification primers and SNPs provides tools to investigate resistin for association with other phenotypes. Received: April 11, 2001 / Accepted: June 11, 2001     

调血脂药对3T3-L1脂肪细胞脂肪水孔蛋白mRNA表达的影响

目的　通过细胞培养研究非诺贝特、洛伐他汀对成熟脂肪细胞脂肪水孔蛋白 (aquaporinadipose,AQPaP)基因表达的影响 ,了解调脂药对AQPaP基因表达有无影响 ,探讨其在肥胖及糖尿病发病中所起作用以及调脂药的药理作用机制。方法　以 10 0 μmol/L、2 5 0 μmol/L非诺贝特及 10 μmol/L洛伐他汀刺激诱导分化第 9天的 3T3 L1脂肪细胞 4 8h ,提取细胞RNA ,运用半定量反转录聚合酶链反应技术 ,检测AQPapmRNA表达量的变化。结果　 10 0 μmol/L非诺贝特刺激脂肪细胞 4 8h后 ,AQPapmRNA表达量有所增加 ,浓度升至 2 5 0 μmol/L ,AQPapmRNA表达量又有下降 ,但各组之间差异无显著性 (P >0 0 5 )。 10 μmol/L洛伐他汀刺激 3T3 L1脂肪细胞4 8h ,与对照组相比 ,AQPapmRNA表达量略有下降 ,但差异无显著性 (P >0 0 5 )。与非诺贝特刺激组相比差异也无显著性差异 (P >0 0 5 )。结论　非诺贝特对脂肪细胞AQPaP基因表达无直接作用。而洛伐他汀对AQPap基因表达也无影响 ,AQPap可能是过氧化物酶体增生剂激活受体 γ(PPAR γ)的一个下游基因     

一氧化氮和脂肪细胞生理及功能调节

作为能量储存主要物质的脂肪组织具有强大的内分泌功能,瘦素、脂联素、胰岛素抵抗素等都可以由脂肪细胞内源性产生。这些激素在机体生理病理调节中发挥着重要作用。最新研究表明,脂肪细胞也有内皮型一氧化氮合酶和诱导型一氧化氮合酶表达,一氧化氮参与脂肪细胞生成分化及能量分解代谢调节,与脂肪代谢异常相关疾病如胰岛素抵抗、肥胖、糖尿病等关系密切。     

前脂肪细胞因子-1对糖脂代谢的影响

前脂肪细胞因子-1(preadipocyte factor1,Pref-1)是脂肪细胞分化早期具有分化抑制作用的分子标志,而脂肪细胞的分化障碍不仅能够导致脂代谢障碍,还可以使糖尿病的易患性增加,导致肥胖、脂肪营养不良、糖尿病等代谢性疾病。本文就Pref-1的结构、表达、其在脂肪细胞分化中的作用及其对糖、脂代谢的影响进行综述。     

大鼠脂肪间充质干细胞体外诱导成骨分化的实验性研究

目的探讨大鼠脂肪间充质干细胞体外分离培养和成骨诱导分化的可行性。方法取6周龄大鼠双侧腹股沟处脂肪，酶鹪法分离培养原代脂肪间充质干细胞，成骨诱导培养18d，检测细胞成骨表型转化：碱性磷酸酶、骨钙素的表达以及细胞矿化细胞外基质的能力。结果大鼠脂肪中能分离培养出一定量的脂肪间充质干细胞，在成骨诱导培养液作用下，可特异性表达成骨分化的标志：碱性磷酸酶、骨钙素，同时也具有矿化细胞外基质的能力。结论大鼠脂肪间充质干细胞可能是一种理想的骨组织工程种子细胞的来源。     

RX781094 a potent and selective alpha 2-adrenergic antagonist. Effects in adipocytes and hepatocytes

The potency and selectivity of RX781094, 2-(2-(1,4-benzodioxanyl]-2-imidazoline HCl, as alpha 1- and alpha 2-adrenergic antagonist was studied using rat hepatocytes and hamster adipocytes. The alpha 1-adrenergic stimulation of ureogenesis produced by epinephrine in rat hepatocytes was slightly diminished by 10(-4) M RX781094. On the contrary the alpha 2-adrenergic effect of epinephrine in hamster adipocytes (inhibition of adenylate cyclase) was antagonized dose-dependently by RX781094. This agent was approximately 10-fold more potent than yohimbine. Radioligand binding studies also showed that RX781094 was more potent and selective than yohimbine at alpha 2-adrenergic sites. It is concluded that RX781094 is a potent and selective alpha 2-adrenergic antagonist.