Adipose cell size changes are associated with a drastic actin remodeling
Adipose cell size changes are associated with a drastic actin remodeling
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DOI：
10.1038/s41598-019-49418-0
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发表时间：
2019-09-10
影响因子：
4.6
通讯作者：
Stenkula, Karin G.
中科院分区：
文献类型：
--
作者：
Hansson, Bjorn;Moren, Bjorn;Stenkula, Karin G.
脂肪组织在调节全身胰岛素敏感性和能量代谢中发挥着重要作用。为了容纳多余的能量，组织通过增加脂肪细胞大小（肥大）和细胞数量（增生）来快速扩张。先前的研究表明，增大、肥大的脂肪细胞对胰岛素的反应较差，并且脂肪细胞的大小可以作为 2 型糖尿病发生的预测因子。在本研究中，我们证明脂肪细胞大小的变化与肌动蛋白细胞骨架的剧烈重塑相关。通过荧光显微镜评估，C57BL6/J 小鼠高脂饮食 (HFD) 喂养 2 周后，原代脂肪细胞的扩张与丝状 (F)-肌动蛋白的急剧增加有关，Rho 激酶活性增加，肌动蛋白调节蛋白的表达发生变化，有利于肌动蛋白聚合。同时，细胞大小的增加与胰岛素反应受损有关，而细胞骨架支架蛋白 IQGAP1 和胰岛素受体底物 (IRS)-1 之间的相互作用保持完整。将 HFD 喂养逆转为食物可以恢复细胞大小、胰岛素反应、肌动蛋白调节蛋白的表达，并减少 F-肌动蛋白丝的数量。我们共同报告了脂肪细胞扩张过程中剧烈的细胞骨架重塑，这一过程可能导致脂肪细胞功能恶化。
Adipose tissue plays a major role in regulating whole-body insulin sensitivity and energy metabolism. To accommodate surplus energy, the tissue rapidly expands by increasing adipose cell size (hypertrophy) and cell number (hyperplasia). Previous studies have shown that enlarged, hypertrophic adipocytes are less responsive to insulin, and that adipocyte size could serve as a predictor for the development of type 2 diabetes. In the present study, we demonstrate that changes in adipocyte size correlate with a drastic remodeling of the actin cytoskeleton. Expansion of primary adipocytes following 2 weeks of high-fat diet (HFD)-feeding in C57BL6/J mice was associated with a drastic increase in filamentous (F)-actin as assessed by fluorescence microscopy, increased Rho- kinase activity, and changed expression of actin-regulating proteins, favoring actin polymerization. At the same time, increased cell size was associated with impaired insulin response, while the interaction between the cytoskeletal scaffolding protein IQGAP1 and insulin receptor substrate (IRS)-1 remained intact. Reversed feeding from HFD to chow restored cell size, insulin response, expression of actin-regulatory proteins and decreased the amount of F-actin filaments. Together, we report a drastic cytoskeletal remodeling during adipocyte expansion, a process which could contribute to deteriorating adipocyte function.