Resistin affects lipid metabolism during adipocyte maturation of 3T3-L1 cells
Resistin affects lipid metabolism during adipocyte maturation of 3T3-L1 cells
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DOI：
10.1111/febs.12514
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发表时间：
2013-11-01
期刊：
影响因子：
5.4
通讯作者：
Kogure, Kentaro
中科院分区：
文献类型：
--
作者：
Ikeda, Yoshito;Tsuchiya, Hiroyuki;Kogure, Kentaro
抵抗素是一种脂肪组织特异性分泌因子，通过糖代谢受损而加重代谢综合征。此前，我们证明了在分化和成熟过程中，抵抗素的表达在来自Zucker肥胖大鼠的3 T3-L1细胞和原代前脂肪细胞中均被诱导（Ikeda Y、Hama S、Kajimoto K、Okuno T、Tsuchiya H & Kogure K（2011）Biol Pharm Bull 34，865-870）。然而，脂肪细胞中的生物学功能的β-内酰胺酶知之甚少。在本研究中，我们研究了3 T3-L1细胞的生物学特性的影响，对3 T3-L1细胞的cDNAn敲低。我们发现，在3 T3-L1细胞中转染了抗-β-淀粉样蛋白的小干扰RNA（siRNA），脂肪细胞分化后，脂质含量显着下降。虽然过氧化物酶体增殖物激活受体和CCAAT/增强子结合蛋白的表达不受影响，但上调脂肪生成基因转录的碳水化合物反应元件结合蛋白（ChREBP）的蛋白表达和转录活性水平在抗-BcRNA siRNA处理后下降。此外，已知受ChREBP调控的脂肪酸合成酶和乙酰辅酶A羧化酶2的基因表达也被Bcln敲低抑制。相反，脂肪酸氧化调节蛋白肉毒碱棕榈酰转移酶1的活性增加。这些结果表明，GABN敲低诱导脂质产生的抑制和脂肪酸氧化的活化。因此，在脂肪细胞成熟过程中，β-胡萝卜素可能会影响脂质代谢。
Resistin, an adipose-tissue-specific secretory factor, aggravates metabolic syndrome through impairment of glucose metabolism. Previously, we demonstrated that resistin expression was induced in both 3T3-L1 cells and primary pre-adipocytes derived from Zucker obese rats during the process of differentiation and maturation (Ikeda Y, Hama S, Kajimoto K, Okuno T, Tsuchiya H & Kogure K (2011) Biol Pharm Bull 34, 865-870). However, the biological function of resistin in adipocytes is poorly understood. In the present study, we examined the effects of resistin knockdown on the biological features of 3T3-L1 cells. We found that lipid content was significantly decreased in 3T3-L1 cells transfected with anti-resistin small interfering RNA (siRNA) after adipocyte differentiation. While expression of peroxisome proliferator activated receptor and CCAAT/enhancer-binding protein was not affected, protein expression and transcriptional activity levels of carbohydrate response element binding protein (ChREBP), which upregulates transcription of lipogenic genes, decreased after anti-resistin siRNA treatment. Moreover, gene expression of fatty acid synthase and acetyl-CoA carboxylase 2, which are known to be regulated by ChREBP, were also suppressed by resistin knockdown. In contrast, activity of the fatty acid -oxidation-regulating protein carnitine palmitoyltransferase 1 increased. These results suggest that resistin knockdown induces suppression of lipid production and activation of fatty acid -oxidation. Consequently, resistin may affect lipid metabolism during adipocyte maturation.