Phenylenediamine derivatives induce GDF-15/MIC-1 and inhibit adipocyte differentiation of mouse 3T3-L1 cells.

Phenylenediamine derivatives induce GDF-15/MIC-1 and inhibit adipocyte differentiation of mouse 3T3-L1 cells.
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苯二胺衍生物诱导 GDF-15/MIC-1 并抑制小鼠 3T3-L1 细胞的脂肪细胞分化。

DOI:
10.1016/j.bbrc.2011.11.103
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发表时间:
2012
影响因子:
3.1
通讯作者:
T. Satoh
T. Satoh
中科院分区:
生物学4区
文献类型:
--
作者:
Mika Yanagitai;T. Kitagawa;K. Okawa;H. Koyama;T. Satoh

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苯二胺衍生物可以作为氢供体,并据报道发挥各种生物学作用,包括对氧化应激的细胞保护作用,可能通过充当抗氧化剂。先前的研究表明,给小鼠喂食此类化合物会减轻其体重,但目前尚不清楚确切的机制。在这里,我们发现,这些化合物抑制小鼠前脂肪细胞,3 T3-L1细胞,成脂肪细胞的体外分化,这表明,至少部分,减少脂肪细胞的产生可能有助于观察到的小鼠体重减轻。接下来,我们进行了阵列分析,发现这些衍生物上调了TGFβ超家族细胞因子GDF-15/MIC-1和细胞因子细胞内下游效应子Trib 3的表达。因此,我们鉴定了这些化合物作为GDF-15/MIC-1的诱导剂,并表明这种诱导可能导致脂肪细胞分化的抑制,这可以解释这些化合物的减肥作用。
Phenylenediamine derivatives can function as a hydrogen donor and reportedly exert various biological actions including cytoprotective effects against oxidative stress, possibly by acting as an antioxidant. Previous studies showed that feeding of such compounds to mice reduced their body weight, but the precise mechanism remains unknown at present. Here, we found that these compounds inhibited the in vitro differentiation of mouse preadipocytes, 3T3-L1 cells, into adipocytes, suggesting that, at least in part, reduced generation of adipocytes might contribute to the observed weight loss in mice. Next, we performed array analysis and found that the expression of GDF-15/MIC-1, which is a TGFβ superfamily cytokine, and Trib 3, an intracellular downstream effector of the cytokines, was up-regulated by these derivatives. Thus, we identified the compounds as inducers of GDF-15/MIC-1 and suggest that such induction may have led to inhibition of adipocyte differentiation, which could account for the weight-loss effect of these compounds.
DOI: 10.1073/pnas.0505723102
发表时间: 2006-01-17
影响因子: 11.1
作者:
Satoh, T;Okamoto, SI;Lipton, SA
通讯作者: Lipton, SA