Wassink A M J, Olijhoek J K, Visseren F L J
Department of Vascular Medicine, University Medical Centre Utrecht, The Netherlands.
Eur J Clin Invest. 2007 Jan;37(1):8-17. doi: 10.1111/j.1365-2362.2007.01755.x.
Despite criticism regarding its clinical relevance, the concept of the metabolic syndrome improves our understanding of both the pathophysiology of insulin resistance and its associated metabolic changes and vascular consequences. Free fatty acids (FFA) and tumour necrosis factor-alpha (TNF-alpha) play prominent roles in the development of insulin resistance by impairing the intracellular insulin signalling transduction pathway. Obesity is an independent risk factor for cardiovascular disease and strongly related to insulin resistance. In case of obesity, FFAs and TNF-alpha are produced in abundance by adipocytes, whereas the production of adiponectin, an anti-inflammatory adipokine, is reduced. This imbalanced production of pro- and anti-inflammatory adipokines, as observed in adipocyte dysfunction, is thought to be the driving force behind insulin resistance. The role of several recently discovered adipokines such as resistin, visfatin and retinol-binding protein (RBP)-4 in the pathogenesis of insulin resistance is increasingly understood. Insulin resistance induces several metabolic changes, including hyperglycaemia, dyslipidaemia and hypertension, all leading to increased cardiovascular risk. In addition, the dysfunctional adipocyte, reflected largely by low adiponectin levels and a high TNF-alpha concentration, directly influences the vascular endothelium, causing endothelial dysfunction and atherosclerosis. Adipocyte dysfunction could therefore be regarded as the common antecedent of both insulin resistance and atherosclerosis and functions as the link between obesity and cardiovascular disease. Targeting the dysfunctional adipocyte may reduce the risk for both cardiovascular disease and the development of type 2 diabetes. Although lifestyle intervention remains the cornerstone of therapy in improving insulin sensitivity and its associated metabolic changes, medical treatment might prove to be important as well.
尽管代谢综合征的临床相关性受到批评，但其概念有助于我们更好地理解胰岛素抵抗的病理生理学及其相关的代谢变化和血管后果。游离脂肪酸（FFA）和肿瘤坏死因子-α（TNF-α）通过损害细胞内胰岛素信号转导途径，在胰岛素抵抗的发生发展中起重要作用。肥胖是心血管疾病的独立危险因素，与胰岛素抵抗密切相关。在肥胖情况下，脂肪细胞大量产生FFA和TNF-α，而抗炎性脂肪因子脂联素的产生则减少。在脂肪细胞功能障碍中观察到的促炎和抗炎脂肪因子的这种不平衡产生，被认为是胰岛素抵抗背后的驱动力。人们越来越了解几种最近发现的脂肪因子，如抵抗素、内脂素和视黄醇结合蛋白（RBP）-4在胰岛素抵抗发病机制中的作用。胰岛素抵抗会引发多种代谢变化，包括高血糖、血脂异常和高血压，所有这些都会增加心血管疾病风险。此外，主要由低脂联素水平和高TNF-α浓度反映的功能失调的脂肪细胞直接影响血管内皮，导致内皮功能障碍和动脉粥样硬化。因此，脂肪细胞功能障碍可被视为胰岛素抵抗和动脉粥样硬化的共同前因，并作为肥胖与心血管疾病之间的联系。针对功能失调的脂肪细胞可能会降低心血管疾病和2型糖尿病发生的风险。尽管生活方式干预仍然是改善胰岛素敏感性及其相关代谢变化的治疗基石，但药物治疗可能也很重要。
