Ronti Tiziana, Lupattelli Graziana, Mannarino Elmo
Internal Medicine, Angiology and Atherosclerosis, Department of Clinical and Experimental Medicine, University of Perugia, Italy.
Clin Endocrinol (Oxf). 2006 Apr;64(4):355-65. doi: 10.1111/j.1365-2265.2006.02474.x.
Adipose tissue secretes bioactive peptides, termed 'adipokines', which act locally and distally through autocrine, paracrine and endocrine effects. In obesity, increased production of most adipokines impacts on multiple functions such as appetite and energy balance, immunity, insulin sensitivity, angiogenesis, blood pressure, lipid metabolism and haemostasis, all of which are linked with cardiovascular disease. Enhanced activity of the tumour necrosis factor and interleukin 6 are involved in the development of obesity-related insulin resistance. Angiotensinogen has been implicated in hypertension and plasminogen activating inhibitor-1 (PAI-1) in impaired fibrinolysis. Other adipokines like adiponectin and leptin, at least in physiological concentrations, are insulin sparing as they stimulate beta oxidation of fatty acids in skeletal muscle. The role of resistin is less understood. It is implicated in insulin resistance in rats, but probably not in humans. Reducing adipose tissue mass, through weight loss in association with exercise, can lower TNF-alpha and IL-6 levels and increase adiponectin concentrations, whereas drugs such as thiazolinediones increase endogenous adiponectin production. In-depth understanding of the pathophysiology and molecular actions of adipokines may, in the coming years, lead to effective therapeutic strategies designed to protect against atherosclerosis in obese patients.
脂肪组织分泌生物活性肽,即所谓的“脂肪因子”,这些因子通过自分泌、旁分泌和内分泌作用在局部和远处发挥作用。在肥胖状态下,大多数脂肪因子的产生增加会影响多种功能,如食欲和能量平衡、免疫、胰岛素敏感性、血管生成、血压、脂质代谢和止血,所有这些都与心血管疾病有关。肿瘤坏死因子和白细胞介素6的活性增强与肥胖相关的胰岛素抵抗的发展有关。血管紧张素原与高血压有关,纤溶酶原激活抑制剂-1(PAI-1)与纤维蛋白溶解受损有关。其他脂肪因子,如脂联素和瘦素,至少在生理浓度下,具有节省胰岛素的作用,因为它们能刺激骨骼肌中脂肪酸的β氧化。抵抗素的作用尚不太清楚。它与大鼠的胰岛素抵抗有关,但可能与人类无关。通过与运动相结合的减肥来减少脂肪组织量,可以降低肿瘤坏死因子-α和白细胞介素-6水平,并增加脂联素浓度,而噻唑烷二酮类药物等药物可增加内源性脂联素的产生。在未来几年,深入了解脂肪因子的病理生理学和分子作用可能会带来旨在保护肥胖患者免受动脉粥样硬化影响的有效治疗策略。