Lymphotoxin β receptor-dependent control of lipid homeostasis
Lymphotoxin β receptor-dependent control of lipid homeostasis
复制标题
DOI：
10.1126/science.1137221
复制
发表时间：
2007-04-13
期刊：
影响因子：
56.9
通讯作者：
Fu, Yang-Xin
中科院分区：
文献类型：
--
作者：
Lo, James C.;Wang, Yugang;Fu, Yang-Xin
高血压是冠心病最重要的危险因素之一，通常与炎症有关。我们确定了主要在淋巴细胞上表达的肿瘤坏死因子细胞因子家族成员-光毒素（LT）和LIGHT，作为控制脂质代谢的关键酶的关键调节剂。T细胞上LIGHT表达的失调导致高胆固醇血症和高胆固醇血症。在低密度脂蛋白受体缺陷的小鼠中，缺乏控制血液中脂质水平的能力，用可溶性光敏素β受体诱饵蛋白抑制LT和LIGHT信号传导减轻了血脂异常。这些结果表明，免疫系统直接影响脂质代谢和LT调节剂可能代表一种新的治疗途径，用于治疗血脂异常。
Hyperlipidemia, one of the most important risk factors for coronary heart disease, is often associated with inflammation. We identified lymphotoxin ( LT) and LIGHT, tumor necrosis factor cytokine family members that are primarily expressed on lymphocytes, as critical regulators of key enzymes that control lipid metabolism. Dysregulation of LIGHT expression on T cells resulted in hypertriglyceridemia and hypercholesterolemia. In low-density lipoprotein receptor-deficient mice, which lack the ability to control lipid levels in the blood, inhibition of LT and LIGHT signaling with a soluble lymphotoxin beta receptor decoy protein attenuated the dyslipidemia. These results suggest that the immune system directly influences lipid metabolism and that LT modulating agents may represent a novel therapeutic route for the treatment of dyslipidemia.