Resveratrol inhibits lipogenesis of 3T3-L1 and SGBS cells by inhibition of insulin signaling and mitochondrial mass increase
Resveratrol inhibits lipogenesis of 3T3-L1 and SGBS cells by inhibition of insulin signaling and mitochondrial mass increase
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DOI：
10.1016/j.bbabio.2016.03.009
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发表时间：
2016-06-01
影响因子：
4.3
通讯作者：
Rousseau, Denis
中科院分区：
文献类型：
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作者：
Li, Shuijie;Bouzar, Celia;Rousseau, Denis
白藜芦醇由于其降低体重和延长寿命的潜力而引起了人们的极大兴趣，通过增加线粒体质量和能量消耗来影响肝脏和肌肉功能。尽管白藜芦醇已经在动物模型中显示出减少脂肪组织质量，但其对脂肪细胞中线粒体质量和网络结构的影响尚未研究。为了这个目的，我们研究了白藜芦醇对两种脂肪细胞生物学体外模型，小鼠3 T3-L1细胞系和人SGBS细胞株的成脂分化过程中线粒体质量增加和重塑的影响。我们证实，白藜芦醇抑制分化脂肪细胞，小鼠和人类的脂肪生成。我们进一步表明，这与抑制通常观察到的线粒体质量增加和线粒体重塑有关。在分子水平上，白藜芦醇的抗脂肪生成作用似乎是通过钝化表达增加和抑制乙酰辅酶A羧化酶（ACC）介导的。这是通过Akt抑制胰岛素诱导的信号传导并通过AMP活化的蛋白激酶维持信号传导的结果之一。白藜芦醇的抗脂肪生成作用进一步通过线粒体ATAD 3的表达水平调节，这与该蛋白作为线粒体生物生成和脂肪生成的重要调节剂的新兴作用一致。我们的数据表明，白藜芦醇通过抑制胰岛素信号传导，线粒体生物合成和脂肪生成来分化前脂肪细胞，并且白藜芦醇诱导的线粒体生物合成和脂质储存的减少有助于动物和人类脂肪组织的体重减轻。(C)2016爱思唯尔B. V.保留所有权利。
Resveratrol is attracting much interest because of its potential to decrease body weight and increase life span, influencing liver and muscle function by increasing mitochondrial mass and energy expenditure. Even though resveratrol was already shown to reduce the adipose tissue mass in animal models, its effects on mitochondrial mass and network structure in adipocytes have not yet been studied. For this purpose, we investigated the effect of resveratrol on mitochondrial mass increase and remodeling during adipogenic differentiation of two in vitro models of adipocyte biology, the murine 3T3-L1 cell line and the human SGBS cell strain. We confirm that resveratrol inhibits lipogenesis in differentiating adipocytes, both mouse and human. We further show that this is linked to inhibition of the normally observed mitochondrial mass increase and mitochondrial remodeling. At the molecular level, the anti-lipogenic effect of resveratrol seems to be mediated by a blunted expression increase and an inhibition of acetyl-CoA carboxylase (ACC). This is one of the consequences of an inhibited insulin-induced signaling via Akt, and maintained signaling via AMP-activated protein kinase. The anti-lipogenic effect of resveratrol is further modulated by expression levels of mitochondrial ATAD3, consistent with the emerging role of this protein as an important regulator of mitochondrial biogenesis and lipogenesis. Our data suggest that resveratrol acts on differentiating preadipocytes by inhibiting insulin signaling, mitochondrial biogenesis, and lipogenesis, and that resveratrol-induced reduction of mitochondrial biogenesis and lipid storage contribute to adipose tissue weight loss in animals and humans. (C) 2016 Elsevier B.V. All rights reserved.