Requirement of Cavin-2 for the expression and stability of IRβ in adequate adipocyte differentiation.
Requirement of Cavin-2 for the expression and stability of IRβ in adequate adipocyte differentiation.
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DOI：
10.1016/j.molmet.2021.101416
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发表时间：
2022-01
影响因子：
8.1
通讯作者：
Matoba S
中科院分区：
文献类型：
--
作者：
Higuchi Y;Ogata T;Nakanishi N;Nishi M;Sakamoto A;Tsuji Y;Tomita S;Matoba S
脂肪生成在维持能量和荷尔蒙平衡方面起着至关重要的作用。Cavin-2是小窝相关蛋白之一，在脂肪细胞中含量丰富，是脂肪形成的主要部位。然而，Cavin-2在脂肪形成中的作用细节仍不清楚。在这里，我们论证了在充分的脂肪细胞分化中，Cavin-2对IRβ的表达和稳定性的要求。Cavin-2基因敲除小鼠(Cavin-2 KO)和野生型(WT)小鼠以高脂饮食(HFD)喂养8周。我们评估了体重、食物摄入量和几种组织。通过葡萄糖和胰岛素耐量试验评估血糖稳态。用Akt磷酸化方法检测附睾白脂肪组织(EWAT)中的胰岛素信号。在体外研究中，我们对脂肪细胞分化、成脂相关基因和胰岛素信号转导进行了研究，以阐明在Cavin-2表达调控下Cavin-2与成脂的关系。Cavin-2 KO小鼠和Cavin-2基因敲除的3T3-L1细胞的eWAT小凹结构减少。Cavin-2通过在脂肪细胞质膜上直接结合来增强胰岛素受体(IR)的稳定性，从而加速胰岛素/IR/Akt信号在含胰岛素溶液刺激的3T3-L1脂肪细胞中的成脂基因表达。IR介导的Akt激活也增强了Cavin-2和IR的表达。Cavin-2基因敲除小鼠表现出胰岛素抵抗并伴有血脂异常，并在HFD后出现病理性肥大的脂肪细胞。Cavin-2通过结合IR和调节胰岛素信号来增强IR的稳定性，从而促进足够的脂肪细胞分化。我们的发现强调了Cavin-2在脂肪生成和脂肪代谢中的关键作用，这可能有助于开发新的病理性肥胖和成脂疾病的治疗方法。在脂肪细胞分化过程中，Cavin-2的表达逐渐增加。Cavin-2基因敲除小鼠的3T3L-1脂肪细胞和eWAT中显示少量的小凹。Cavin-2通过IR稳定正向调节脂肪生成。高脂饮食的Cavin-2基因敲除小鼠表现出胰岛素抵抗和血脂异常。
Adipogenesis plays an essential role in maintaining energy and hormonal balance. Cavin-2, one of the caveolae-related proteins, is abundant in adipocytes, the leading site of adipogenesis. However, the details of the roles of Cavin-2 in adipogenesis remain unknown. Here, we demonstrate the requirement of Cavin-2 for the expression and stability of IRβ in adequate adipocyte differentiation. Cavin-2 knockout (Cavin-2 KO) and wild-type (WT) mice were fed with a high-fat diet (HFD) for 8 weeks. We evaluated body weight, food intake, and several tissues. Glucose homeostasis was assessed by glucose and insulin tolerance tests. Insulin signaling in epididymal white adipose tissue (eWAT) was determined by Akt phosphorylation. In vitro study, we evaluated adipocyte differentiation, adipogenesis-related genes, and insulin signaling to clarify the relationship between Cavin-2 and adipogenesis under the manipulation of Cavin-2 expression. Caveolae structure decreased in eWAT of Cavin-2 KO mice and Cavin-2 knockdown 3T3-L1 cells. Cavin-2 enhanced the stability of insulin receptor (IR) through direct association at the plasma membrane in adipocytes, resulting in accelerated insulin/IR/Akt signaling-induced adipogenic gene expression in insulin-containing solution-stimulated 3T3-L1 adipocytes. IR-mediated Akt activation also enhanced Cavin-2 and IR expression. Cavin-2 knockout mice showed insulin resistance with dyslipidemia and pathological hypertrophic adipocytes after a HFD. Cavin-2 enhances IR stability through binding IR and regulates insulin signaling, promoting adequate adipocyte differentiation. Our findings highlight the pivotal role of Cavin-2 in adipogenesis and lipid metabolism, which may help to develop novel therapies for pathological obesity and adipogenic disorders. Cavin-2 expression is increased progressively during adipocyte differentiation. Cavin-2 knockout shows little caveolae in 3T3L-1 adipocytes and eWAT of mice. Cavin-2 positively regulates adipogenesis through IR stabilization. Cavin-2 knockout mice with a high-fat diet show insulin resistance and dyslipidemia.
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影响因子：
16.6
作者：
通讯作者：
--
DOI：
10.1083/jcb.200903053
发表时间：
2009-06-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bastiani M;Liu L;Hill MM;Jedrychowski MP;Nixon SJ;Lo HP;Abankwa D;Luetterforst R;Fernandez-Rojo M;Breen MR;Gygi SP;Vinten J;Walser PJ;North KN;Hancock JF;Pilch PF;Parton RG
通讯作者：
Parton RG
影响因子：
5.8
作者：
Kim, C. A.;Delepine, Marc;Magre, Jocelyne
通讯作者：
Magre, Jocelyne
影响因子：
4
作者：
Birsoy, Kivanc;Festuccia, William T.;Laplante, Mathieu
通讯作者：
Laplante, Mathieu
DOI：
10.1073/pnas.2536828100
发表时间：
2003-12-23
影响因子：
11.1
作者：
He, WM;Barak, Y;Evans, RM
通讯作者：
Evans, RM