Adipocyte-specific protein tyrosine phosphatase 1B deletion increases lipogenesis, adipocyte cell size and is a minor regulator of glucose homeostasis.
Adipocyte-specific protein tyrosine phosphatase 1B deletion increases lipogenesis, adipocyte cell size and is a minor regulator of glucose homeostasis.
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DOI：
10.1371/journal.pone.0032700
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Delibegović M
中科院分区：
文献类型：
--
作者：
Owen C;Czopek A;Agouni A;Grant L;Judson R;Lees EK;Mcilroy GD;Göransson O;Welch A;Bence KK;Kahn BB;Neel BG;Mody N;Delibegović M
蛋白酪氨酸磷酸酶1B(PTP1B)是瘦素和胰岛素信号转导的关键负性调节因子，与肥胖呈正相关，并参与胰岛素抵抗。PTP1B全球缺失通过增强大脑中的瘦素信号和增加肝脏和肌肉中的胰岛素信号来改善饮食诱导的肥胖和葡萄糖动态平衡。然而，PTP1B在脂肪细胞中的作用尚不清楚，研究表明，脂肪PTP1B缺乏对体重和胰岛素抵抗有好处、有害或没有影响(S)。为了明确脂肪细胞PTP1B在体重调节和血糖稳态中的作用，利用脂联素启动子驱动Cre重组酶的表达，建立了脂肪细胞特异性PTP1B基因敲除小鼠(ADIP-crePTP1B−/−)。饲喂脂肪的PTP1B−/−小鼠显示脂肪细胞增大，尽管与对照组相比，它们的体重/脂肪和血糖稳态相似。与对照组相比，高脂饮食喂养的脂肪增殖型PTP1B−/−小鼠在体重/肥胖方面没有差异，但显示出更大的脂肪细胞，循环中葡萄糖和瘦素水平增加，瘦素敏感性降低，基础脂肪生成增加。这与胰岛素受体(IR)和Akt/PKB磷酸化减少、造脂基因表达增加和低氧诱导因子-1-α(Hif-1α)表达增加有关。脂肪细胞特异的PTP1B缺失并不能有益地调控信号通路，调节脂肪细胞中的葡萄糖稳态、脂肪代谢或脂肪因子的分泌。此外，PTP1B似乎不是脂肪细胞IR的主要负调控因子。
Protein tyrosine phosphatase 1B (PTP1B), a key negative regulator of leptin and insulin signaling, is positively correlated with adiposity and contributes to insulin resistance. Global PTP1B deletion improves diet-induced obesity and glucose homeostasis via enhanced leptin signaling in the brain and increased insulin signaling in liver and muscle. However, the role of PTP1B in adipocytes is unclear, with studies demonstrating beneficial, detrimental or no effect(s) of adipose-PTP1B-deficiency on body mass and insulin resistance. To definitively establish the role of adipocyte-PTP1B in body mass regulation and glucose homeostasis, adipocyte-specific-PTP1B knockout mice (adip-crePTP1B−/−) were generated using the adiponectin-promoter to drive Cre-recombinase expression. Chow-fed adip-crePTP1B−/− mice display enlarged adipocytes, despite having similar body weight/adiposity and glucose homeostasis compared to controls. High-fat diet (HFD)-fed adip-crePTP1B−/− mice display no differences in body weight/adiposity but exhibit larger adipocytes, increased circulating glucose and leptin levels, reduced leptin sensitivity and increased basal lipogenesis compared to controls. This is associated with decreased insulin receptor (IR) and Akt/PKB phosphorylation, increased lipogenic gene expression and increased hypoxia-induced factor-1-alpha (Hif-1α) expression. Adipocyte-specific PTP1B deletion does not beneficially manipulate signaling pathways regulating glucose homeostasis, lipid metabolism or adipokine secretion in adipocytes. Moreover, PTP1B does not appear to be the major negative regulator of the IR in adipocytes.
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影响因子：
7.7
作者：
Delibegovic M;Zimmer D;Kauffman C;Rak K;Hong EG;Cho YR;Kim JK;Kahn BB;Neel BG;Bence KK
通讯作者：
Bence KK
影响因子：
15.9
作者：
Banno, Ryoichi;Zimmer, Derek;Bence, Kendra K.
通讯作者：
Bence, Kendra K.
影响因子：
4.8
作者：
Bai, YL;Zhang, SY;Kim, KH
通讯作者：
Kim, KH
影响因子：
29
作者：
Eguchi J;Wang X;Yu S;Kershaw EE;Chiu PC;Dushay J;Estall JL;Klein U;Maratos-Flier E;Rosen ED
通讯作者：
Rosen ED
影响因子：
16.2
作者：
Katsuki, A;Sumida, Y;Adachi, Y
通讯作者：
Adachi, Y