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STAT6 促进罗格列酮治疗的小鼠肝和脂肪炎性细胞中 PKM2 的双向调节。

STAT6 promotes bi-directional modulation of PKM2 in liver and adipose inflammatory cells in rosiglitazone-treated mice.

机构信息

Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1 Rue Michel Servet, Geneva 4, Switzerland

出版信息

Sci Rep. 2013;3:2350. doi: 10.1038/srep02350.

DOI:10.1038/srep02350
PMID:23917405
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3734444/
Abstract

STAT6 interacts with PPARγ to elicit macrophage polarization towards an anti-inflammatory, insulin-sensitizing phenotype. Mice deficient in STAT6 display liver lipid accumulation (hepatosteatosis). Rosiglitazone (RSG), a PPARγ agonist, ameliorates hepatosteatosis and enhances insulin sensitivity. To elucidate the role of STAT6 in PPARγ action on hepatosteatosis we compared liver proteomes of RSG-treated wild type and STAT6-deficient mice and we identified pyruvate kinase M2 (PKM2), a glycolysis and proliferation-regulating enzyme that displayed STAT6-dependent expression. RSG induced PKM2 within inflammatory cells in liver but suppressed its expression in adipose tissue. RSG diminished hepatosteatosis and oxidative stress, enhanced fat accumulation and improved insulin sensitivity in STAT6-deficient mice. Our data reveal a complex interaction between STAT6 and PPARγ in the regulation of liver and adipose tissue lipid depot distribution and design STAT6 as a novel link between inflammatory cell metabolism and adipocyte and hepatocyte function.

摘要

STAT6 与 PPARγ 相互作用，诱导巨噬细胞向抗炎、胰岛素敏化表型极化。STAT6 缺陷小鼠显示肝脏脂质积累（脂肪变性）。PPARγ 激动剂罗格列酮 (RSG) 可改善脂肪变性并增强胰岛素敏感性。为了阐明 STAT6 在 PPARγ 对脂肪变性作用中的作用，我们比较了 RSG 处理的野生型和 STAT6 缺陷型小鼠的肝蛋白质组，并鉴定出丙酮酸激酶 M2 (PKM2)，一种糖酵解和增殖调节酶，其表达依赖于 STAT6。RSG 在肝脏的炎症细胞中诱导 PKM2，但在脂肪组织中抑制其表达。RSG 减少了 STAT6 缺陷小鼠的脂肪变性和氧化应激，增加了脂肪堆积，并改善了胰岛素敏感性。我们的数据揭示了 STAT6 和 PPARγ 在调节肝脏和脂肪组织脂质库分布中的复杂相互作用，并将 STAT6 设计为炎症细胞代谢与脂肪细胞和肝细胞功能之间的新联系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf2/3734444/d6103e3516af/srep02350-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf2/3734444/345d3fcf8122/srep02350-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf2/3734444/5a177d5baea7/srep02350-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf2/3734444/ed0492393fd1/srep02350-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf2/3734444/65c8a714d77e/srep02350-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf2/3734444/f919a0f85f88/srep02350-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf2/3734444/d6103e3516af/srep02350-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf2/3734444/345d3fcf8122/srep02350-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf2/3734444/dd6ce4fb7f5e/srep02350-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf2/3734444/5a177d5baea7/srep02350-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf2/3734444/ed0492393fd1/srep02350-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf2/3734444/65c8a714d77e/srep02350-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf2/3734444/f919a0f85f88/srep02350-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf2/3734444/d6103e3516af/srep02350-f7.jpg

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