Fat-specific Protein 27 ( FSP27) Interacts with Adipose Triglyceride Lipase ( ATGL) to Regulate Lipolysis and Insulin Sensitivity in Human Adipocytes
Fat-specific Protein 27 ( FSP27) Interacts with Adipose Triglyceride Lipase ( ATGL) to Regulate Lipolysis and Insulin Sensitivity in Human Adipocytes
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DOI：
10.1074/jbc.m113.539890
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发表时间：
2014-04-25
影响因子：
4.8
通讯作者：
Puri, Vishwajeet
中科院分区：
文献类型：
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作者：
Grahn, Tan Hooi Min;Kaur, Rajween;Puri, Vishwajeet
背景：FSP 27耗竭增加基础和刺激的脂解。结果：FSP 27通过氨基酸120-220与ATGL相互作用，调节人脂肪细胞中的脂解和甘油三酯储存。结论：FSP 27抑制ATGL介导的脂肪分解，并保护脂肪细胞免受游离脂肪酸损伤的胰岛素信号转导。重要性：在脂肪细胞中，脂解是一个高度调节的过程，涉及激素信号、脂滴相关蛋白和脂肪酶。新的脂滴相关蛋白的发现增加了目前脂解模型的复杂性。在这项研究中，我们使用培养的人脂肪细胞，以证明脂肪特异性蛋白27（FSP 27），脂肪细胞中大量表达的蛋白质，调节基础和刺激脂解与脂肪甘油三酯脂肪酶（ATGL，也称为desnutrin或PNPLA 2）相互作用。我们鉴定了FSP 27的核心结构域，氨基酸120-220，其与ATGL相互作用以抑制其脂解功能并促进甘油三酯储存。我们还确定了FSP 27在脂肪细胞中游离脂肪酸诱导的胰岛素抵抗中的作用。人脂肪细胞中的FSP 27耗竭增加了脂解，并通过降低AKT磷酸化来抑制胰岛素信号传导。然而，通过消耗ATGL或表达外源全长FSP 27或氨基酸120-220来减少脂解保护人脂肪细胞免受游离脂肪酸对胰岛素信号传导的不利影响。在来自ATGL KO小鼠的胚胎成纤维细胞中，外源性游离脂肪酸不影响胰岛素敏感性。我们的研究结果表明FSP 27-ATGL相互作用在调节人脂肪细胞中的脂解、甘油三酯积累和胰岛素信号传导中起着至关重要的作用。
Background: FSP27 depletion increases both basal and stimulated lipolysis. Results: FSP27 interacts with ATGL via amino acids 120-220 to regulate lipolysis and triglyceride storage in human adipocytes. Conclusion: FSP27 inhibits ATGL-mediated lipolysis and protects adipocytes against free fatty acid-impaired insulin signaling. Significance: The novel lipolytic regulation shown here may lead to new treatments for insulin resistance.In adipocytes, lipolysis is a highly regulated process involving hormonal signals, lipid droplet-associated proteins, and lipases. The discovery of new lipid droplet-associated proteins added complexity to the current model of lipolysis. In this study, we used cultured human adipocytes to demonstrate that fat-specific protein 27 (FSP27), an abundantly expressed protein in adipocytes, regulates both basal and stimulated lipolysis by interacting with adipose triglyceride lipase (ATGL, also called desnutrin or PNPLA2). We identified a core domain of FSP27, amino acids 120-220, that interacts with ATGL to inhibit its lipolytic function and promote triglyceride storage. We also defined the role of FSP27 in free fatty acid-induced insulin resistance in adipocytes. FSP27 depletion in human adipocytes increased lipolysis and inhibited insulin signaling by decreasing AKT phosphorylation. However, reducing lipolysis by either depletion of ATGL or expression of exogenous full-length FSP27 or amino acids 120-220 protected human adipocytes against the adverse effects of free fatty acids on insulin signaling. In embryonic fibroblasts derived from ATGL KO mice, exogenous free fatty acids did not affect insulin sensitivity. Our results demonstrate a crucial role for FSP27-ATGL interactions in regulating lipolysis, triglyceride accumulation, and insulin signaling in human adipocytes.