Serum amyloid A1 levels and amyloid deposition following a high-fat diet challenge in transgenic mice overexpressing hepatic serum amyloid A1
Serum amyloid A1 levels and amyloid deposition following a high-fat diet challenge in transgenic mice overexpressing hepatic serum amyloid A1
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DOI：
10.1139/apnm-2015-0369
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发表时间：
2016-06-01
影响因子：
3.4
通讯作者：
Ryoo, Zae Young
中科院分区：
文献类型：
--
作者：
Jang, Woo Young;Jeong, Jain;Ryoo, Zae Young
血清淀粉样蛋白A（SAA）是肝脏中的急性时相反应蛋白，而SAA 1是淀粉样蛋白A淀粉样变性的主要前体蛋白。这种淀粉样变性已被报道为慢性炎症性疾病如关节炎、狼疮和克罗恩病的并发症。肥胖还与慢性、低度炎症和持续、升高的SAA 1水平有关。然而，升高的循环SAA 1对代谢紊乱及其并发症的贡献尚不清楚。此外，在最近的几项研究中，过表达SAA 1的转基因（TG）小鼠被喂食高脂饮食（HFD）相对较短的时间，没有发现SAA 1上调和代谢紊乱之间的关系。因此，我们产生了在肝脏中过表达SAA 1的TG小鼠，用HFD攻击这些小鼠，并研究了升高的SAA 1水平的影响。持续升高的SAA 1水平与HFD 16周后肝脏中的代谢参数和局部细胞因子表达相关。此外，长期消费（52周）的HFD与葡萄糖耐量受损和SAA 1水平升高，并导致全身SAA 1衍生的淀粉样蛋白沉积在肾脏，肝脏和脾脏的TG小鼠。因此，我们得出结论，在长期HFD暴露下升高的SAA 1水平导致广泛的SAA 1衍生的淀粉样蛋白沉积，这可能有助于与HFD诱导的肥胖和代谢紊乱相关的并发症。
Serum amyloid A (SAA) is an acute-phase response protein in the liver, and SAA1 is the major precursor protein involved in amyloid A amyloidosis. This amyloidosis has been reported as a complication in chronic inflammatory conditions such as arthritis, lupus, and Crohn's disease. Obesity is also associated with chronic, low-grade inflammation and sustained, elevated levels of SAA1. However, the contribution of elevated circulating SAA1 to metabolic disturbances and their complications is unclear. Furthermore, in several recent studies of transgenic (TG) mice overexpressing SAA1 that were fed a high-fat diet (HFD) for a relatively short period, no relationship was found between SAA1 up-regulation and metabolic disturbances. Therefore, we generated TG mice overexpressing SAA1 in the liver, challenged these mice with an HFD, and investigated the influence of elevated SAA1 levels. Sustained, elevated levels of SAA1 were correlated with metabolic parameters and local cytokine expression in the liver following 16 weeks on the HFD. Moreover, prolonged consumption (52 weeks) of the HFD was associated with impaired glucose tolerance and elevated SAA1 levels and resulted in systemic SAA1-derived amyloid deposition in the kidney, liver, and spleen of TG mice. Thus, we concluded that elevated SAA1 levels under long-term HFD exposure result in extensive SAA1-derived amyloid deposits, which may contribute to the complications associated with HFD-induced obesity and metabolic disorders.