Jialal Ishwarlal, Devaraj Sridevi
Section of Endocrinology, VA Medical Center, Mather and California North-State University College of Medicine, 9700 West Taron Drive, Elk Grove, CA 95757, USA, Fax: +916-686-7310.
Department of Pathology and Immunology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA.
Horm Mol Biol Clin Investig. 2018 Jan 20;33(1):hmbci-2017-0074. doi: 10.1515/hmbci-2017-0074.
Metabolic syndrome (MetS) is a common global problem that comprises the cardio-metabolic cluster and predisposes to both diabetes and cardiovascular diseases. Although the pathogenic mechanisms have not been elucidated, both increased inflammation and insulin resistance play a pivotal role. It appears that both monocyte/macrophages and adipose tissue (AT) conspire to accentuate both the pro-inflammatory state and increased insulin resistance. Whilst there are scant data on visceral adipose tissue (VAT) and epicardial adipose tissue (EAT) biology, there are data on subcutaneous adipose tissue (SAT) dysregulation. There is a significant increase in macrophages and crown-like structures in the SAT of patients with MetS. With respect to adipokines, there is an increase in plasma leptin, plasminogen activator inhibitor-1, retinol-binding protein-4 (RBP-4), chemerin, serum amyloid-A, C-reactive protein (CRP), interleukin-1, -6, -8, lipopolysaccharide, fetuin A (FetA) and a decrease in adiponectin and omentin-1. All of the abnormalities in plasma were also confirmed for SAT-secreted adipokines except for adiponectin and RBP-4 which derive largely from VAT. As many of these biomediators correlate with both insulin resistance and increased inflammation, we can posit that dysregulation of SAT is detrimental and contributes to both the pathogenesis of MetS and its sequalae. Furthermore, as future directions, much work is needed with respect to VAT/EAT biology, autophagy, sirtuins, the gut microbiome, browning of AT, to further elucidate this common syndrome and identify potential therapeutic targets to forestall its serious complications.
代谢综合征（MetS）是一个常见的全球性问题，它包含心血管代谢簇，易引发糖尿病和心血管疾病。尽管其致病机制尚未阐明，但炎症增加和胰岛素抵抗均起着关键作用。似乎单核细胞/巨噬细胞和脂肪组织（AT）共同加剧了促炎状态和胰岛素抵抗的增加。虽然关于内脏脂肪组织（VAT）和心外膜脂肪组织（EAT）生物学的数据很少，但有关于皮下脂肪组织（SAT）失调的数据。代谢综合征患者的SAT中巨噬细胞和冠状结构显著增加。关于脂肪因子，血浆瘦素、纤溶酶原激活物抑制剂-1、视黄醇结合蛋白-4（RBP-4）、chemerin、血清淀粉样蛋白A、C反应蛋白（CRP）、白细胞介素-1、-6、-8、脂多糖、胎球蛋白A（FetA）增加，而脂联素和网膜素-1减少。除脂联素和RBP-4（它们主要来源于VAT）外，SAT分泌的脂肪因子在血浆中的所有异常情况也得到了证实。由于许多这些生物介质与胰岛素抵抗和炎症增加均相关，我们可以假定SAT失调是有害的，并促成了代谢综合征的发病机制及其后遗症。此外，作为未来的研究方向，在VAT/EAT生物学、自噬、沉默调节蛋白、肠道微生物群、AT褐变方面还需要做大量工作，以进一步阐明这一常见综合征，并确定潜在的治疗靶点以预防其严重并发症。
