Homocysteine inhibits adipogenesis in 3T3-L1 preadipocytes.
Homocysteine inhibits adipogenesis in 3T3-L1 preadipocytes.
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同型半胱氨酸抑制3T3-L1前脂肪细胞中的脂肪形成。
DOI：
10.1258/ebm.2011.011234
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Song Z
中科院分区：
文献类型：
--
作者：
Wang Z;Dou X;Yao T;Song Z
高同型半胱氨酸血症（Hyperhomocysteinemia，HHcy）是高血压、糖尿病、酒精性肝病等多种疾病的特征性代谢异常。新的证据表明，脂肪组织有助于高同型半胱氨酸和同型半胱氨酸（Hcy）反过来影响脂肪组织的功能。然而，Hcyon脂肪形成的具体作用知之甚少。本研究以3 T3-L1前脂肪细胞为研究对象，探讨了同型半胱氨酸对脂肪形成过程的影响及其机制。将融合的小鼠胚胎3 T3-L1前脂肪细胞（D 0）暴露于分化混合物三天（D3）。然后，将细胞转移到含胰岛素的培养基中，并每两天重新补料一次。在第7天通过油红O染色脂滴证实脂肪细胞的成熟。在D 0或D3向培养基中加入外源性Hcy。在第7天，测量脂肪形成指数。我们的数据表明，这两个Hcy添加方案抑制脂肪形成过程中，证明了减少脂质积累和下调脂肪细胞蛋白2和过氧化物酶体增殖物激活受体γ（PPAR-gamma）的基因表达，这意味着Hcy有丝分裂克隆扩增（MCE）阶段和分化阶段的抑制作用。进一步研究表明，Hcy通过降低视网膜母细胞瘤蛋白磷酸化水平和E2 F-1蛋白表达而抑制MCE。为了阐明PPAR-gamma在Hcy诱导的脂肪生成抑制中的重要作用，我们采用了一种特异性PPAR-gamma激动剂罗格列酮来代替胰岛素诱导脂肪生成。我们的研究结果表明，同型半胱氨酸抑制罗格列酮诱导的脂肪形成在一个类似的方式，因为这是由胰岛素，这表明抑制PPAR-gamma反式激活是至关重要的同型半胱氨酸诱导的抑制作用，对脂肪形成。两者合计，我们的数据表明，同型半胱氨酸抑制3 T3-L1前脂肪细胞的脂肪形成和抑制PPAR-gamma的反式作用可能，至少部分，有助于抑制效果。
Hyperhomocysteinemia (HHcy) is a characteristic metabolic abnormality in several pathological conditions, including hypertension, diabetes and alcoholic liver disease. Emerging evidence indicates that adipose tissue contributes to HHcy and homocysteine (Hcy) conversely affects adipose tissue function. However, the specific effect of Hcyon adipogenesis is poorly understood. In the present study, we investigated the effects and mechanisms of Hcy on adipogenic process using 3T3-L1 preadipocytes, a well-established in vitro model for the study of adipogenesis. Confluent mouse embryo 3T3-L1 preadipocytes (D0) were exposed to differentiation cocktail for three days (D3). Then, cells were transferred to insulin-containing medium and re-fed every two days. Maturation of adipocytes was confirmed by Oil Red O staining of lipid droplets on day 7. Exogenous Hcy was added to the culture medium on either D0 or D3. At day 7, adipogenesis indices were measured. Our data indicated that both Hcy addition protocols suppressed adipogenic process, evidenced by decreased lipid accumulation and downregulated gene expressions of adipocyte protein 2 and peroxisome proliferator-activated receptor gamma (PPAR-gamma), implying that Hcy exerted inhibitory effects on both mitotic clonal expansion (MCE) stage and differentiation stage. Further study showed that Hcy suppresses MCE via decreasing retinoblastoma protein phosphorylation and E2F-1 protein expression. To delineate the critical involvement of PPAR-gamma in Hcy-induced suppression on adipogenesis, we employed rosiglitazone, a specific PPAR-gamma agonist, to replace insulin for the inductive stimulus of adipogenesis. Our results showed that Hcy suppressed rosiglitazone-induced adipogenesis in a similar fashion as this by insulin, suggesting that inhibition of PPAR-gamma transactivation was critically involved in the Hcy-induced inhibitory effect on adipogenesis. Taken together, our data indicate that Hcy suppressed adipogenesis in 3T3-L1 preadipocytes and the inhibition of PPAR-gamma transactivity may, at least partially, contribute to the suppressive effect.
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影响因子：
25.7
作者：
Medici, Valentina;Peerson, Janet M.;Stabler, Sally P.;French, Samuel W.;Gregory, Jesse F., III;Virata, Maria Catrina;Albanese, Antony;Bowlus, Christopher L.;Devaraj, Sridevi;Panacek, Edward A.;Rahim, Nazir;Richards, John R.;Rossaro, Lorenzo;Halsted, Charles H.
通讯作者：
Halsted, Charles H.
影响因子：
2.9
作者：
Sen U;Tyagi SC
通讯作者：
Tyagi SC
DOI：
10.1073/pnas.0306743102
发表时间：
2005-04-26
影响因子：
11.1
作者：
Jones, JR;Barrick, C;Magnuson, MA
通讯作者：
Magnuson, MA
影响因子：
5.7
作者：
de Jong, SC;van den Berg, M;Stehouwer, CDA
通讯作者：
Stehouwer, CDA
影响因子：
16.2
作者：
Meigs, JB;Jacques, PF;Wilson, PWF
通讯作者：
Wilson, PWF