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应对完美风暴:肥胖症中的生物标志物及心血管代谢风险的病理生理学。

Addressing the Perfect Storm: Biomarkers in Obesity and Pathophysiology of Cardiometabolic Risk.

机构信息

Nutrition, Immunity and Metabolism Start-up Lab, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.

Friedman School of Nutrition Science & Policy, Tufts University, Boston, MA.

出版信息

Clin Chem. 2018 Jan;64(1):142-153. doi: 10.1373/clinchem.2017.275172. Epub 2017 Nov 14.

Abstract

BACKGROUND

The worldwide rise of obesity has provoked intensified research to better understand its pathophysiology as a means for disease prevention. Several biomarkers that may reflect various pathophysiological pathways that link obesity and cardiometabolic diseases have been identified over the past decades.

CONTENT

We summarize research evidence regarding the role of established and novel obesity-related biomarkers, focusing on recent epidemiological evidence for detrimental associations with cardiometabolic diseases including obesity-related cancer. The reviewed biomarkers include biomarkers of glucose-insulin homeostasis (insulin, insulin-like growth factors, and C-peptide), adipose tissue biomarkers (adiponectin, omentin, apelin, leptin, resistin, and fatty-acid-binding protein-4), inflammatory biomarkers (C-reactive protein, interleukin 6, tumor necrosis factor α), and omics-based biomarkers (metabolites and microRNAs).

SUMMARY

Although the evidence for many classical obesity biomarkers, including adiponectin and C-reactive protein (CRP), in disease etiology has been initially promising, the evidence for a causal role in humans remains limited. Further, there has been little demonstrated ability to improve disease prediction beyond classical risk factors. In the era of "precision medicine," there is an increasing interest in novel biomarkers, and the extended list of potentially promising biomarkers, such as adipokines, cytokines, metabolites, and microRNAs, implicated in obesity may bring new promise for improved, personalized prevention. To further evaluate the role of obesity-related biomarkers as etiological and early-disease-prediction targets, well-designed studies are needed to evaluate temporal associations, replicate findings, and test clinical utility of novel biomarkers. In particular, studies to determine the therapeutic implications of novel biomarkers beyond established metabolic risk factors are highly warranted.

摘要

背景

肥胖在全球范围内的流行促使人们加强了对其病理生理学的研究,以期更好地预防相关疾病。过去几十年间,人们已经发现了几种可能反映肥胖与心血管代谢疾病之间关联的不同病理生理途径的生物标志物。

内容

我们总结了有关既定和新型肥胖相关生物标志物作用的研究证据,重点关注了最近与心血管代谢疾病(包括肥胖相关癌症)具有不利关联的流行病学证据。综述的生物标志物包括葡萄糖-胰岛素稳态的标志物(胰岛素、胰岛素样生长因子和 C 肽)、脂肪组织标志物(脂联素、网膜素、Apelin、瘦素、抵抗素和脂肪酸结合蛋白-4)、炎症标志物(C 反应蛋白、白细胞介素 6、肿瘤坏死因子-α)和基于组学的生物标志物(代谢物和 microRNAs)。

总结

尽管包括脂联素和 C 反应蛋白(CRP)在内的许多经典肥胖生物标志物在疾病病因学方面的最初证据很有前景,但在人类中这些标志物因果关系的证据仍然有限。此外,在改善疾病预测方面,这些标志物除了经典风险因素外,其能力也有限。在“精准医学”时代,人们对新型生物标志物越来越感兴趣,而与肥胖相关的具有潜在前景的新型生物标志物(如脂肪因子、细胞因子、代谢物和 microRNAs)的扩展列表,可能为改善个性化预防带来新的希望。为了进一步评估肥胖相关生物标志物作为病因和早期疾病预测靶点的作用,需要进行精心设计的研究来评估时间关联、复制发现并测试新型生物标志物的临床实用性。特别是,确定新型生物标志物除了既定代谢风险因素之外的治疗意义的研究非常有必要。

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