Liu Roy, Pulliam Daniel A, Liu Yuhong, Salmon Adam B
The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; Departments of Cellular & Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Redox Biol. 2015 Dec;6:401-408. doi: 10.1016/j.redox.2015.07.014. Epub 2015 Sep 3.
Once thought only as storage for excess nutrients, adipose tissue has been shown to be a dynamic organ implicated in the regulation of many physiological processes. There is emerging evidence supporting differential roles for visceral and subcutaneous white adipose tissue in maintaining health, although how these roles are modulated by the aging process is not clear. However, the proposed beneficial effects of subcutaneous fat suggest that targeting maintenance of this tissue could lead to healthier aging. In this study, we tested whether alterations in adipose function with age might be associated with changes in oxidative stress. Using visceral and subcutaneous adipose from C57BL/6 mice, we discovered effects of both age and depot location on markers of lipolysis and adipogenesis. Conversely, accumulation of oxidative damage and changes in enzymatic antioxidant expression with age were largely similar between these two depots. The activation of each of the stress signaling pathways JNK and MAPK/ERK was relatively suppressed in subcutaneous adipose tissue suggesting reduced sensitivity to oxidative stress. Similarly, pre-adipocytes from subcutaneous adipose were significantly more resistant than visceral-derived cells to cell death caused by oxidative stress. Cellular respiration in visceral-derived cells was dramatically higher than in cells derived from subcutaneous adipose despite little evidence for differences in mitochondrial density. Together, our data identify molecular mechanisms by which visceral and subcutaneous adipose differ with age and suggest potential targetable means to preserve healthy adipose aging.
脂肪组织曾一度仅被视为储存多余营养物质的场所，但现已证明它是一个动态器官，参与多种生理过程的调节。越来越多的证据支持内脏白色脂肪组织和皮下白色脂肪组织在维持健康方面具有不同作用，尽管这些作用如何受到衰老过程的调节尚不清楚。然而，皮下脂肪的潜在有益作用表明，针对该组织的维持可能会带来更健康的衰老。在本研究中，我们测试了脂肪功能随年龄的变化是否可能与氧化应激的变化相关。利用C57BL/6小鼠的内脏脂肪和皮下脂肪，我们发现年龄和储存部位对脂肪分解和脂肪生成标志物均有影响。相反，这两个储存部位随年龄增长的氧化损伤积累和酶促抗氧化剂表达变化在很大程度上相似。应激信号通路JNK和MAPK/ERK在皮下脂肪组织中的激活相对受到抑制，表明对氧化应激的敏感性降低。同样，皮下脂肪来源的前脂肪细胞比内脏来源的细胞对氧化应激引起的细胞死亡具有显著更高的抗性。尽管几乎没有证据表明线粒体密度存在差异，但内脏来源细胞的细胞呼吸明显高于皮下脂肪来源的细胞。总之，我们的数据确定了内脏脂肪和皮下脂肪随年龄变化的分子机制，并提出了潜在的可靶向手段来维持健康的脂肪衰老。
