Obesity-induced remodeling of the adipose tissue elastin network is independent of the metalloelastase MMP-12.
Obesity-induced remodeling of the adipose tissue elastin network is independent of the metalloelastase MMP-12.
复制标题
肥胖引起的脂肪组织弹性蛋白网络重塑不依赖于金属弹性蛋白酶 MMP-12。
DOI：
10.1080/21623945.2015.1027848
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发表时间：
2015
期刊：
影响因子：
3.3
通讯作者：
Lumeng,CareyN
中科院分区：
文献类型：
--
作者：
Martinez-Santibanez,Gabriel;Singer,Kanakadurga;Cho,KaeWon;DelProposto,JenniferL;Mergian,Taleen;Lumeng,CareyN
细胞外基质(ECM)在维持足够的脂肪组织功能和代谢调节中起着重要作用。在这里，我们研究了一种相对未被探索的脂肪组织ECM成分，弹性蛋白的组织及其对饮食诱导的小鼠肥胖的反应。此外，我们还探讨了肥胖症患者脂肪组织细胞外基质重塑过程中巨噬细胞金属弹性蛋白酶-12的调节和需求。在内脏脂肪库中，弹性蛋白纤维形成网状网络，随着饮食导致的肥胖而变得更加致密。相比之下，皮下脂肪库中的弹性蛋白纤维在组织上更呈线性，并与脂肪组织巨噬细胞(ATM)密切相关。我们发现，MMP12主要由ATM产生，短期和长期的高脂饮食刺激和脂解诱导的快速重塑都可以诱导MMP12的产生。这与非ATM人群中只有在慢性肥胖后才会进一步诱导的Mmp14和Timp1形成鲜明对比。我们研究了肥胖的转基因Mmp12−/−小鼠，发现饮食诱导的肥胖患者细胞外基质基因的基因表达增加，但在代谢参数、弹性蛋白基质密度或脂肪组织炎症方面几乎没有显著差异。总之，这些研究揭示了弹性蛋白基质的结构和饮食诱导的调节，并表明基质金属蛋白酶-12不是弹性蛋白基质重塑或肥胖引起的代谢功能障碍所必需的。
The extracellular matrix (ECM) plays important roles in maintaining adequate adipose tissue function and in metabolic regulation. Here we have examined the organization of a relatively unexplored adipose tissue ECM component, elastin and its response to diet induced obesity in mice. Additionally, we have explored the regulation and requirement of macrophage metalloelastase, MMP-12, in adipose tissue ECM remodeling in obesity. In visceral fat depots, elastin fibers form a mesh-like net that becomes denser with diet-induced obesity. In contrast, the elastin fibers in subcutaneous adipose depots are more linear in organization, and are tightly associated with adipose tissue macrophages (ATMs). We found thatMmp12is produced predominantly by ATMs and can be induced with both short- and long-term high fat diet challenge and rapid remodeling induced by lipolysis. This contrasts withMmp14andTimp1which are further induced only after chronic obesity in non-ATM populations. We examined obese transgenicMmp12−/−mice and found an increase in gene expression of ECM genes with diet-induced obesity, but showed few significant differences in metabolic parameters, elastin matrix density, or in adipose tissue inflammation. Together, these studies reveal the architecture and diet-induced regulation of the elastin matrix and suggest that MMP-12 is not required for elastin matrix remodeling or for the metabolic dysfunction that occurs with obesity.