کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2040110 1073098 2016 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Nucleic Acid-Targeting Pathways Promote Inflammation in Obesity-Related Insulin Resistance
ترجمه فارسی عنوان
القاء القایی در مقاومت به انسولین مرتبط با چاقی باعث افزایش میزان نوشیدنی اسید می شود
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم کشاورزی و بیولوژیک (عمومی)
چکیده انگلیسی


• Obesity promotes increased release and decreased clearance of nucleic acid antigens
• Aberrant handling of nucleic acid and related antigens results in autoantibodies
• Excess nucleic acids worsen metabolism through VAT macrophages and liver pDCs
• Inhibiting TLR7/9 improves obesity-related inflammation and glucose homeostasis

SummaryObesity-related inflammation of metabolic tissues, including visceral adipose tissue (VAT) and liver, are key factors in the development of insulin resistance (IR), though many of the contributing mechanisms remain unclear. We show that nucleic-acid-targeting pathways downstream of extracellular trap (ET) formation, unmethylated CpG DNA, or ribonucleic acids drive inflammation in IR. High-fat diet (HFD)-fed mice show increased release of ETs in VAT, decreased systemic clearance of ETs, and increased autoantibodies against conserved nuclear antigens. In HFD-fed mice, this excess of nucleic acids and related protein antigens worsens metabolic parameters through a number of mechanisms, including activation of VAT macrophages and expansion of plasmacytoid dendritic cells (pDCs) in the liver. Consistently, HFD-fed mice lacking critical responders of nucleic acid pathways, Toll-like receptors (TLR)7 and TLR9, show reduced metabolic inflammation and improved glucose homeostasis. Treatment of HFD-fed mice with inhibitors of ET formation or a TLR7/9 antagonist improves metabolic disease. These findings reveal a pathogenic role for nucleic acid targeting as a driver of metabolic inflammation in IR.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 16, Issue 3, 19 July 2016, Pages 717–730
نویسندگان
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