Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medyków 18, PL 40-752 Katowice, Poland.
Pharmacol Rep. 2009 Nov-Dec;61(6):1134-45. doi: 10.1016/s1734-1140(09)70176-8.
Because of methodological limitations and conflicting results of studies conducted thus far, the possible involvement of human adipose tissue in pleiotropic effects of statins and fibrates requires better understanding. Samples of visceral and subcutaneous adipose tissue obtained from 23 mixed dyslipidemic patients and 23 normolipidemic subjects were treated in vitro for 48 h with atorvastatin, fenofibric acid or both these agents. Visceral and subcutaneous fat of mixed dyslipidemic patients released more leptin, resistin, interleukin-6, tumor necrosis factor alpha (TNFalpha and plasminogen activator inhibitor-1 (PAI-1), and less adiponectin than respective adipose tissue of patients without lipid abnormalities. In both groups of patients, visceral and subcutaneous tissue varied in the amount of secreted adipokines. In dyslipidemic patients both drugs administered alone affected adipose tissue adiponectin and resistin secretion. Additionally, atorvastatin decreased PAI-1 while fenofibric acid reduced leptin release. A combined administration of atorvastatin and fenofibric acid changed the release of all studied markers by visceral fat but did not affect interleukin-6 and TNFalpha release by subcutaneous tissue. In normolipidemic subjects the effect on adipokine release was more pronounced in visceral fat, in which it was strongest if the drugs were given together. Adipose tissue hormonal activity differs between mixed dyslipidemic and normolipidemic patients and between visceral and subcutaneous adipose tissue. Atorvastatin and fenofibrate exhibit their pleiotropic effects in part by changing the adipokine release by human adipose tissue, regardless of its origin. These effects are stronger in patients with mixed dyslipidemia and are particularly pronounced if atorvastatin and fenofibric acid are given together.
由于方法学上的限制以及迄今为止进行的研究结果相互矛盾，人类脂肪组织在他汀类药物和贝特类药物的多效性作用中的可能参与需要更好地理解。从 23 例混合性血脂异常患者和 23 例血脂正常患者中获得的内脏和皮下脂肪组织样本在体外用阿托伐他汀、非诺贝特或这两种药物处理 48 小时。混合性血脂异常患者的内脏和皮下脂肪释放的瘦素、抵抗素、白细胞介素-6、肿瘤坏死因子-α（TNF-α）和纤溶酶原激活物抑制剂-1（PAI-1）较多，脂代谢异常患者的相应脂肪组织释放的脂联素较少。在两组患者中，内脏和皮下脂肪组织分泌的脂肪细胞因子数量不同。在血脂异常患者中，单独使用这两种药物均影响脂肪组织脂联素和抵抗素的分泌。此外，阿托伐他汀降低了 PAI-1，而非诺贝特降低了瘦素的释放。阿托伐他汀和非诺贝特联合给药改变了内脏脂肪释放的所有研究标志物，但不影响皮下组织释放白细胞介素-6 和 TNF-α。在血脂正常的受试者中，这种对脂肪细胞因子释放的影响在内脏脂肪中更为明显，如果药物一起使用，则效果最强。混合性血脂异常患者和血脂正常患者的脂肪组织激素活性不同，内脏和皮下脂肪组织之间也存在差异。阿托伐他汀和非诺贝特通过改变人脂肪组织的脂肪细胞因子释放来发挥其多效性作用，而与脂肪组织的来源无关。这些作用在混合性血脂异常患者中更强，如果同时给予阿托伐他汀和非诺贝特，则作用更为明显。
