The Lundberg Laboratory for Diabetes Research, Center of Excellence for Metabolic and Cardiovascular Research, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
J Atheroscler Thromb. 2010 Apr 30;17(4):332-41. doi: 10.5551/jat.3939. Epub 2010 Feb 3.
Metabolic syndrome is associated with dysfunctional adipose tissue that is most likely a consequence of the enlargement of adipocytes and infiltration of macrophages into adipose tissue. Obesity and ectopic lipid deposition are major risk factors for diseases ranging from insulin resistance to type 2 diabetes and atherosclerosis. Enlargement of adipocytes, due to impaired adipocyte differentiation, leads to a chronic state of inflammation in the adipocytes and adipose tissue with a reduction in the secretion of adiponectin and increase in the secretion of proinflammatory cytokines such as interleukin (IL)-6, IL-8 and monocyte chemoattractant protein (MCP)-1. The secretion of cytokines like tumour necrosis factor (TNF)- alpha, mainly from macrophages, enhances local inflammation. These proinflammatory cytokines might also substantially affect cardiovascular function and morphology. Furthermore, a proinflammatory state in adipose tissue can lead to local insulin resistance with an impaired inhibitory effect of insulin on the release of FFAs and endothelial dysfunction that clearly promotes cardiovascular diseases and type 2 diabetes. The underlying mechanisms of ectopic fat accumulation in various tissues and the impact on metabolic syndrome and its association with insulin resistance are discussed.
代谢综合征与功能失调的脂肪组织有关，而脂肪组织功能失调很可能是由于脂肪细胞增大和巨噬细胞浸润脂肪组织所致。肥胖和异位脂质沉积是从胰岛素抵抗到 2 型糖尿病和动脉粥样硬化等疾病的主要危险因素。由于脂肪细胞分化受损导致脂肪细胞增大，会导致脂肪细胞和脂肪组织发生慢性炎症，使脂联素分泌减少，促炎细胞因子（如白细胞介素-6、白细胞介素-8 和单核细胞趋化蛋白-1）分泌增加。肿瘤坏死因子（TNF）-α等细胞因子主要由巨噬细胞分泌，会增强局部炎症。这些促炎细胞因子也可能对心血管功能和形态产生重大影响。此外，脂肪组织的促炎状态可导致局部胰岛素抵抗，减弱胰岛素对游离脂肪酸释放的抑制作用和内皮功能障碍，这显然会促进心血管疾病和 2 型糖尿病的发生。本文还讨论了各种组织中异位脂肪积累的潜在机制及其对代谢综合征的影响，以及与胰岛素抵抗的关系。
