三丁基锡可增强巨噬细胞炎症和脂肪分解,导致脂肪组织功能障碍。

IF 3 Q2 ENDOCRINOLOGY & METABOLISM Journal of the Endocrine Society Pub Date : 2024-10-25 eCollection Date: 2024-10-29 DOI:10.1210/jendso/bvae187
Richard C Chang, Ryan Scott Whitlock, Erika Joloya, Kaitlin Thanh To, Yikai Huang, Bruce Blumberg
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引用次数: 0

摘要

三丁基锡(TBT)是一种广泛应用于工业和商业领域的合成化学品。事实证明,接触三丁基锡化合物会导致肥胖。妊娠期接触三丁基锡化合物会导致接触者(F1、F2)和未接触者(F3、F4)的白色脂肪组织体积增大,这就是转代遗传的一个例子。三丁基锡化合物部分是通过增加白色脂肪细胞的数量和体积、改变多能间充质基质干细胞的命运使其倾向于脂肪细胞系、改变脂肪因子的分泌以及调节染色质结构来产生这些效应的。脂肪组织常住巨噬细胞是脂肪组织的关键调节因子;然而,三丁基锡化合物对脂肪组织巨噬细胞的影响仍不清楚。在此,我们研究了三丁基锡化合物对巨噬细胞的影响及其对脂肪细胞功能的影响。三丁基锡化合物能明显增强小鼠骨髓巨噬细胞中棕榈酸酯诱导的炎症基因表达,而核受体过氧化物酶体增殖激活受体γ的拮抗作用能减弱这种效应。经三丁基锡化合物处理的巨噬细胞可减少由间质基质干细胞分化而成的白色脂肪细胞中的脂质积累,同时增加脂肪分解基因的表达。最后,祖先暴露于三丁基锡化合物会增加暴露(F2)和未暴露(F3)世代的脂肪组织常驻巨噬细胞中的 Tnf 表达,这表明暴露于三丁基锡化合物会导致遗传性脂肪组织巨噬细胞炎症倾向,从而操纵脂肪组织功能。这些发现为了解肥胖症中脂肪细胞和脂肪组织巨噬细胞之间的相互作用提供了新的视角,进一步确定了三丁基锡化合物等肥胖致病因子在肥胖相关代谢紊乱发病中的作用。
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Tributyltin Enhances Macrophage Inflammation and Lipolysis, Contributing to Adipose Tissue Dysfunction.

Tributyltin (TBT) is a synthetic chemical widely used in industrial and commercial applications. TBT exposure has been proven to elicit obesogenic effects. Gestational exposure led to increased white adipose tissue depot size in exposed (F1, F2) animals and in unexposed generations (F3, F4), an example of transgenerational inheritance. TBT exerts these effects in part by increasing the number and size of white adipocytes, altering the fate of multipotent mesenchymal stromal stem cells to favor the adipocyte lineage, altering adipokine secretion, and modulating chromatin structure. Adipose tissue resident macrophages are critical regulators in adipose tissue; however, the effects of TBT on adipose tissue macrophages remained unclear. Here we investigated the effects of TBT on macrophages and consequent impacts on adipocyte function. TBT significantly enhanced palmitate-induced inflammatory gene expression in mouse bone marrow derived macrophages and this effect was attenuated by the antagonizing action of the nuclear receptor peroxisome proliferator activated receptor gamma. TBT-treated macrophages decreased lipid accumulation in white adipocytes differentiated from mesenchymal stromal stem cells accompanied by increased expression of lipolysis genes. Lastly, ancestral TBT exposure increased Tnf expression in adipose tissue resident macrophages in both exposed (F2) and unexposed (F3) generations, suggesting that TBT exposure led to an inherited predisposition toward inflammatory adipose tissue macrophages that can manipulate adipose tissue function. These findings provide new insights into the interplay between adipocytes and adipose tissue macrophages in obesity, further establishing a role for obesogens such as TBT in the development of obesity-related metabolic disorders.

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来源期刊
Journal of the Endocrine Society
Journal of the Endocrine Society Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
5.50
自引率
0.00%
发文量
2039
审稿时长
9 weeks
期刊最新文献
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