Yang Rong-Ze, Lee Mi-Jeong, Hu Hong, Pollin Toni I, Ryan Alice S, Nicklas Barbara J, Snitker Soren, Horenstein Richard B, Hull Kristen, Goldberg Nelson H, Goldberg Andrew P, Shuldiner Alan R, Fried Susan K, Gong Da-Wei
Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA.
PLoS Med. 2006 Jun;3(6):e287. doi: 10.1371/journal.pmed.0030287.
Obesity is associated with low-grade chronic inflammation, and serum markers of inflammation are independent risk factors for cardiovascular disease (CVD). However, the molecular and cellular mechanisms that link obesity to chronic inflammation and CVD are poorly understood.
Acute-phase serum amyloid A (A-SAA) mRNA levels, and A-SAA adipose secretion and serum levels were measured in obese and nonobese individuals, obese participants who underwent weight-loss, and persons treated with the insulin sensitizer rosiglitazone. Inflammation-eliciting activity of A-SAA was investigated in human adipose stromal vascular cells, coronary vascular endothelial cells and a murine monocyte cell line. We demonstrate that A-SAA was highly and selectively expressed in human adipocytes. Moreover, A-SAA mRNA levels and A-SAA secretion from adipose tissue were significantly correlated with body mass index (r = 0.47; p = 0.028 and r = 0.80; p = 0.0002, respectively). Serum A-SAA levels decreased significantly after weight loss in obese participants (p = 0.006), as well as in those treated with rosiglitazone (p = 0.033). The magnitude of the improvement in insulin sensitivity after weight loss was significantly correlated with decreases in serum A-SAA (r = -0.74; p = 0.034). SAA treatment of vascular endothelial cells and monocytes markedly increased the production of inflammatory cytokines, e.g., interleukin (IL)-6, IL-8, tumor necrosis factor alpha, and monocyte chemoattractant protein-1. In addition, SAA increased basal lipolysis in adipose tissue culture by 47%.
A-SAA is a proinflammatory and lipolytic adipokine in humans. The increased expression of A-SAA by adipocytes in obesity suggests that it may play a critical role in local and systemic inflammation and free fatty acid production and could be a direct link between obesity and its comorbidities, such as insulin resistance and atherosclerosis. Accordingly, improvements in systemic inflammation and insulin resistance with weight loss and rosiglitazone therapy may in part be mediated by decreases in adipocyte A-SAA production.
肥胖与低度慢性炎症相关，炎症血清标志物是心血管疾病（CVD）的独立危险因素。然而，将肥胖与慢性炎症及心血管疾病联系起来的分子和细胞机制仍知之甚少。
在肥胖和非肥胖个体、接受减肥的肥胖参与者以及接受胰岛素增敏剂罗格列酮治疗的人群中，测量急性期血清淀粉样蛋白A（A-SAA）的mRNA水平、A-SAA在脂肪组织中的分泌及血清水平。在人脂肪基质血管细胞、冠状动脉血管内皮细胞和小鼠单核细胞系中研究A-SAA的炎症引发活性。我们证明A-SAA在人脂肪细胞中高度且选择性表达。此外，A-SAA的mRNA水平及脂肪组织中的A-SAA分泌与体重指数显著相关（分别为r = 0.47；p = 0.028和r = 0.80；p = 0.0002）。肥胖参与者减肥后血清A-SAA水平显著降低（p = 0.006），接受罗格列酮治疗的参与者也是如此（p = 0.033）。减肥后胰岛素敏感性改善的程度与血清A-SAA的降低显著相关（r = -0.74；p = 0.034）。用SAA处理血管内皮细胞和单核细胞可显著增加炎性细胞因子的产生，如白细胞介素（IL）-6、IL-8、肿瘤坏死因子α和单核细胞趋化蛋白-1。此外，SAA使脂肪组织培养中的基础脂肪分解增加47%。
A-SAA是人体内一种促炎和促脂解的脂肪因子。肥胖时脂肪细胞中A-SAA表达增加表明它可能在局部和全身炎症以及游离脂肪酸产生中起关键作用，并且可能是肥胖与其合并症（如胰岛素抵抗和动脉粥样硬化）之间的直接联系。因此，减肥和罗格列酮治疗导致的全身炎症和胰岛素抵抗的改善可能部分是由脂肪细胞A-SAA产生的减少介导的。
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