Acute-phase serum amyloid A: an inflammatory adipokine and potential link between obesity and its metabolic complications.
Acute-phase serum amyloid A: an inflammatory adipokine and potential link between obesity and its metabolic complications.
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DOI：
10.1371/journal.pmed.0030287
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发表时间：
2006-06
期刊：
影响因子：
15.8
通讯作者：
Gong, Da-Wei
中科院分区：
文献类型：
--
作者：
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
肥胖与低度慢性炎症有关，炎症的血清标志物是心血管疾病（CVD）的独立危险因素。然而，人们对肥胖与慢性炎症和心血管疾病之间的分子和细胞机制知之甚少。测量了肥胖和非肥胖个体、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患者的急性期血清淀粉样蛋白 A (A-SAA) mRNA 水平以及 A-SAA 脂肪分泌和血清水平。在人脂肪基质血管细胞、冠状血管内皮细胞和鼠单核细胞系中研究了 A-SAA 的炎症诱发活性。我们证明 A-SAA 在人类脂肪细胞中高度选择性表达。此外，A-SAA mRNA 水平和脂肪组织的 A-SAA 分泌量与体重指数显着相关（分别为 r = 0.47；p = 0.028 和 r = 0.80；p = 0.0002）。肥胖参与者（p = 0.006）以及接受罗格列酮治疗的参与者（p = 0.033）体重减轻后，血清 A-SAA 水平显着下降。减肥后胰岛素敏感性改善的程度与血清 A-SAA 的降低显着相关（r = -0.74；p = 0.034）。 SAA 处理血管内皮细胞和单核细胞显着增加炎症细胞因子的产生，例如白细胞介素 (IL)-6、IL-8、肿瘤坏死因子 α 和单核细胞趋化蛋白-1。此外，SAA 使脂肪组织培养物中的基础脂肪分解增加了 47%。 A-SAA 是人类的一种促炎和脂肪分解脂肪因子。肥胖中脂肪细胞 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发挥关键作用，并且可能是肥胖与其合并症（例如胰岛素抵抗和动脉粥样硬化）之间的直接联系。因此，体重减轻和罗格列酮治疗对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。肥胖通常会改变个体的整体新陈代谢，进而导致糖尿病、高血压等并发症，并增加患心血管疾病（心脏和血管疾病，如中风或心脏病）的风险。炎症与心血管疾病之间存在密切联系，科学家们现在认为肥胖可能会导致持续的低水平炎症，这就是许多肥胖者出现心血管问题的原因。通过更好地了解肥胖、炎症和心血管疾病之间的联系，科学家们希望能够找到可以用于肥胖人群的药物，以降低心脏病发作和中风的风险。此前的研究表明，血液中一种由炎症引起的称为A-SAA的物质可能是炎症与心血管疾病之间的“缺失环节”，因为个体的A-SAA基线水平与心血管疾病的风险相关（换句话说，A-SAA越高，患心血管疾病的风险越高）。在这项新研究中，研究人员想知道肥胖者患心血管疾病的风险较高是否是因为他们血液中的 A-SAA 水平较高。他们发现肥胖者血液中的 A-SAA 含量较高。 A-SAA 似乎是在脂肪细胞（或脂肪细胞）中产生，然后释放到血液中。肥胖者的脂肪细胞数量较多，这本身就可以解释血液中 A-SAA 水平较高的原因，但研究人员还发现，肥胖者的平均脂肪细胞比瘦人的脂肪细胞产生和分泌的 A-SAA 水平更高。当研究人员研究减肥人群时，他们发现 A-SAA 水平随着减肥而下降，这与新陈代谢的改善有关。然后，他们研究了接受糖尿病药物罗格列酮（已知可以减轻炎症）的肥胖个体。他们发现，尽管这些人的体重没有减轻，但随着新陈代谢的改善，他们的 A-SAA 水平却下降了。为了了解 A-SAA 可能导致炎症和糖尿病的机制，研究人员发现接触 A-SAA 可以刺激许多不同细胞（包括血管细胞）中促炎症分子的激活。它还可以刺激细胞分解脂肪储存并释放脂肪，这可能导致代谢并发症并最终导致糖尿病。与其他研究的类似结果一起，本文的研究结果表明，A-SAA 可能会促进炎症，而肥胖个体中 A-SAA 水平升高可能会导致慢性低水平炎症状态，从而使他们面临更高的心血管并发症风险。作者推测，降低血液中 A-SAA 水平的药物可能有助于治疗肥胖患者（降低心脏病和中风的风险）。然而，正如他们承认的那样，需要进行更多研究来确定 A-SAA 确实是肥胖和炎症之间的因果关系，以及它是否发挥着重要作用，然后才能将其视为有希望的药物靶点。请通过此摘要的在线版本访问这些网站：http://dx.doi.org/10.1371/journal.pmed.0030287。 • MedlinePlus 关于肥胖和心血管疾病的页面 • 美国疾病控制与预防中心关于肥胖和心血管疾病的页面 • 关于肥胖和心血管疾病的维基百科页面（注：维基百科是任何人都可以编辑的免费互联网百科全书） 肥胖个体中较高水平的急性期血清淀粉样蛋白 A (A-SAA)（一种促炎脂肪因子）可能会导致慢性低水平炎症状态，从而使他们面临更高的心血管并发症风险。
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. Obesity often alters an individual's overall metabolism, which in turn leads to complications like diabetes, high blood pressure, and an increased risk of cardiovascular disease (disease of the heart and blood vessels, such as stroke or heart attacks). Having established a strong link between inflammation and cardiovascular disease, scientists now think that obesity might cause persistent low-level inflammation, and that this is the reason for the cardiovascular problems seen in many obese people. By better understanding the links between obesity, inflammation, and cardiovascular disease, the hope is that scientists may be able to find medications that can be given to obese people to reduce their risk of heart attacks and strokes. Previous research had suggested that a substance in the blood called A-SAA, which is raised by inflammation, might be a “missing link” between inflammation and cardiovascular disease, since an individual's baseline level of A-SAA is associated with the risk for cardiovascular disease (in other words, the higher the A-SAA, the higher the risk of cardiovascular disease). In the new study, researchers wanted to know whether the reason that obese people have a higher risk of cardiovascular disease is because they have higher blood levels of A-SAA. They found that obese people had higher levels of A-SAA in their blood. A-SAA appears to be produced in fat cells (or adipocytes) and then released into the blood. Obese people have higher numbers of fat cells, which could by itself account for the higher blood levels of A-SAA, but the researchers also found that the average fat cell from an obese individual produces and secretes higher levels of A-SAA than fat cells from lean individuals. When the researchers studied people who underwent weight loss, they found that A-SAA levels fell in response to weight loss, and this was associated with improvements in their metabolism. They then studied obese individuals who received the diabetes drug rosiglitazone (which is known to reduce inflammation). They found that even though these individuals did not lose weight, their A-SAA levels dropped as their metabolism improved. Trying to get at the mechanisms by which A-SAA might cause inflammation and diabetes, the researchers found that exposure to A-SAA can stimulate the activation of proinflammation molecules in a number of different cells, including blood vessel cells. It can also stimulate cells to break down fat stores and release fats, which could lead to metabolic complications and ultimately contribute to diabetes. Together with similar results from other studies, the findings here suggest that A-SAA could promote inflammation, and that elevated levels of A-SAA in obese individuals could contribute to the chronic low-level inflammatory state that puts them at higher risk for cardiovascular complications. The authors speculate that drugs that reduce the blood levels of A-SAA might be useful as treatments for obese patients (to lower their risk of heart attacks and strokes). However, as they acknowledge, additional studies are needed to establish that A-SAA is indeed a causal link between obesity and inflammation and whether it plays a major role before it could be considered a promising drug target. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030287. • MedlinePlus pages on obesity and cardiovascular disease • US Centers for Disease Control and Prevention pages on obesity and cardiovascular disease • Wikipedia pages on obesity and cardiovascular disease (note: Wikipedia is a free Internet encyclopedia that anyone can edit) Higher levels of Acute-phase serum amyloid A (A-SAA), a proinflammatory adipokine, in obese individuals may contribute to the chronic low-level inflammatory state that puts them at higher risk for cardiovascular complications.
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影响因子：
82.9
作者：
Arkan, MC;Hevener, AL;Karin, M
通讯作者：
Karin, M
影响因子：
16.2
作者：
Isomaa, B;Almgren, P;Groop, L
通讯作者：
Groop, L
DOI：
10.3181/00379727-156-39916
发表时间：
1977-01-01
影响因子：
--
作者：
LAVAU, M;SUSINI, C;GREENWOOD, MRC
通讯作者：
GREENWOOD, MRC
影响因子：
64.8
作者：
Jiang, CY;Ting, AT;Seed, B
通讯作者：
Seed, B
肿瘤坏死因子-α的脂肪表达--在与肥胖相关的胰岛素抵抗中的直接作用
影响因子：
56.9
作者：
HOTAMISLIGIL, GS;SHARGILL, NS;SPIEGELMAN, BM
通讯作者：
SPIEGELMAN, BM