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海藻糖诱导的 SIRT1/AMPK 激活调节 SREBP-1c/PPAR-α 以减轻衰老肝脏中的脂质积累。

Trehalose-induced SIRT1/AMPK activation regulates SREBP-1c/PPAR-α to alleviate lipid accumulation in aged liver.

机构信息

Department of Clinical Biochemistry, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.

Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2024 Feb;397(2):1061-1070. doi: 10.1007/s00210-023-02644-w. Epub 2023 Aug 15.

DOI:10.1007/s00210-023-02644-w
PMID:37581638
Abstract

Aging is associated with a disturbance in the regulation of the metabolic function of the liver, which increases the risk of liver and systemic diseases. Trehalose, a natural disaccharide, has been identified to reduce dyslipidemia, hepatic steatosis, and glucose intolerance. However, the roles of trehalose on lipid metabolism in aged liver are unclear which was investigated in this study. Thirty-two male Wistar rats were randomly allocated into four groups (n = 8). Two groups of aged (24 months) and young (4 months) rats were administered 2% trehalose solution orally for 30 days. Control groups of aged and young rats did not receive any treatment. At the end of the treatment period, blood samples and liver tissues were collected. Then the expression of SIRT1, AMPK, SREBP-1c, and PPAR-α and the level of AMPK phosphorylation (p-AMPK) were quantified by real-time polymerase chain reaction and western blotting. Moreover, biochemical parameters and the histopathology of livers were evaluated. Trehalose supplementation increased the level of SIRT1, p-AMPK, and PPAR-α, whereas the level of SREBP-1c was diminished in the liver of old animals. In addition, treatment with trehalose improved histopathological features of senescent livers. Taken together, our results show that old rats developed lipogenesis in the liver which was alleviated with trehalose. Therefore, trehalose may be an effective intervention to reduce the progression of aging-induced liver diseases.

摘要

衰老是与肝脏代谢功能调节紊乱有关,这增加了肝脏和全身性疾病的风险。海藻糖,一种天然双糖,已被确定可以降低血脂异常、肝脂肪变性和葡萄糖不耐受。然而,海藻糖对衰老肝脏脂质代谢的作用尚不清楚,本研究对此进行了探讨。32 只雄性 Wistar 大鼠被随机分为四组(n = 8)。两组老年(24 个月)和年轻(4 个月)大鼠经口给予 2%海藻糖溶液 30 天。老年和年轻对照组大鼠未接受任何治疗。在治疗期末,采集血样和肝组织。然后通过实时聚合酶链反应和蛋白质印迹定量检测 SIRT1、AMPK、SREBP-1c 和 PPAR-α 的表达以及 AMPK 磷酸化(p-AMPK)水平。此外,还评估了生化参数和肝脏的组织病理学。海藻糖补充增加了老年动物肝脏中 SIRT1、p-AMPK 和 PPAR-α 的水平,而 SREBP-1c 的水平则降低。此外,海藻糖治疗改善了衰老肝脏的组织病理学特征。总之,我们的研究结果表明,老年大鼠肝脏发生了脂肪生成,而海藻糖可以缓解这种情况。因此,海藻糖可能是一种有效的干预措施,可以减缓衰老引起的肝脏疾病的进展。

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