肥胖相关新型生物标志物的研究及展望

Research advances in new obesity-related biomarkers

肥胖是一种体脂过多或分布异常的病理状态,是引发2型糖尿病、代谢症候群、心脑血管疾病、非酒精性脂肪肝,甚至某些类型的癌症等重大疾病的重要诱因。大量研究表明,诸多脂肪因子(adipokines)和肝细胞因子(hepatokines)水平在肥胖时发生显著变化,通过检测此类因子的动态水平可以预测或评估疾病的发生、发展及其并发症情况,并评判其治疗效果。在目前已发现的众多脂肪因子和肝细胞因子中,大量人体和动物研究一致发现在肥胖状态下脂联素(adiponectin)水平下降,而成纤维生长因子21(FGF21)和生长分化因子15(GDF15)则上升。它们不仅可作为肥胖诊断和监控的生物标志物,亦参与了肥胖的病理生理过程,是潜在的治疗靶点。其中脂联素已广泛应用于肥胖相关代谢病的风险评估,而FGF21和GDF15长效类似物或受体激动剂则被用于治疗肥胖相关疾病并且已开始相关的临床试验。文章着重讨论脂联素、FGF21和GDF15在肥胖及其并发症中的地位及其之间的密切关系,并展望这3种新型肥胖生物标志物的研究发展方向和临床应用前景。

Obesity,characterized by excessive or abnormal accumulation of adipose tissues,is a major risk factor for a cluster of chronic diseases,including type 2 diabetes(T2 D),metabolic syndrome,cardiovascular and cerebrovascular diseases,non-alcoholic fatty liver disease(NAFLD)and some types of cancers.Recent studies have identified a large number of adipose-secreted adipokines and liver-secreted hepatokines as objective blood biomarkers for monitoring the onset and progression of obesity and its related complications,as well as for evaluating the therapeutic offect.Among them,animal studies and clinical investigations in different ethnic groups have consistently observed decreased circulating level of adiponectin,but increased serum levels of fibroblast growth factor 21(FGF21)and growth differentiation factor 15(GDF15)in obesity,and changes in their circulating concentrations are closely associated with the pathogenesis of obesityrelated complications.Serum adiponectin has now been used clinically as a biomarker for risk prediction of T2 D,whilst the mimetics and agonists of FGF21 and GDF15 are being developed for the treatment of obesity and NAFLD.This review aims to summarize the recent research advances on these three-emerging obesity-related biomarkers,and to discuss the current challenges and future perspectives for their clinical applications as diagnostic biomarkers or/and therapeutic targets.