Metabolic Dysregulation and Adipose Tissue Fibrosis: Role of Collagen VI
Metabolic Dysregulation and Adipose Tissue Fibrosis: Role of Collagen VI
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DOI：
10.1128/mcb.01300-08
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发表时间：
2009-03-15
影响因子：
5.3
通讯作者：
Scherer, Philipp E.
中科院分区：
文献类型：
--
作者：
Khan, Tayeba;Muise, Eric S.;Scherer, Philipp E.
脂肪细胞嵌入独特的细胞外基质中，其主要功能是提供机械支撑，此外还参与各种信号传导事件。在脂肪组织扩张过程中，细胞外基质需要重塑以适应脂肪细胞的生长。在这里，我们证明了糖尿病状态下脂肪组织中几种细胞外基质成分的普遍上调，因此暗示“脂肪组织纤维化”是代谢受到挑战的脂肪细胞的标志。 VI 型胶原蛋白是脂肪组织中高度丰富的细胞外基质成分。 VI 型胶原蛋白的缺乏会导致单个脂肪细胞不受抑制的扩张，并且与全身能量稳态的显着改善相关，无论是在高脂肪饮食暴露还是在产后背景下。总的来说，我们的数据表明，削弱脂肪细胞的细胞外支架可以使其在正能量平衡状态下无压力扩张，从而与改善炎症状况相关。因此，脂肪组织中细胞外基质成分的不成比例的积累可能不仅仅是代谢挑战条件下的附带现象，而且还可能直接导致在热量摄入过多的状态下无法扩大脂肪组织质量。
Adipocytes are embedded in a unique extracellular matrix whose main function is to provide mechanical support, in addition to participating in a variety of signaling events. During adipose tissue expansion, the extracellular matrix requires remodeling to accommodate adipocyte growth. Here, we demonstrate a general upregulation of several extracellular matrix components in adipose tissue in the diabetic state, therefore implicating "adipose tissue fibrosis" as a hallmark of metabolically challenged adipocytes. Collagen VI is a highly enriched extracellular matrix component of adipose tissue. The absence of collagen VI results in the uninhibited expansion of individual adipocytes and is paradoxically associated with substantial improvements in whole-body energy homeostasis, both with high-fat diet exposure and in the ob/ob background. Collectively, our data suggest that weakening the extracellular scaffold of adipocytes enables their stress-free expansion during states of positive energy balance, which is consequently associated with an improved inflammatory profile. Therefore, the disproportionate accumulation of extracellular matrix components in adipose tissue may not be merely an epiphenomenon of metabolically challenging conditions but may also directly contribute to a failure to expand adipose tissue mass during states of excess caloric intake.