Selenium Deficiency Induces Pathological Cardiac Lipid Metabolic Remodeling and Inflammation
Selenium Deficiency Induces Pathological Cardiac Lipid Metabolic Remodeling and Inflammation
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缺硒诱导病理性心脏脂质代谢重塑和炎症
DOI：
10.1002/mnfr.202100644
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发表时间：
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影响因子：
5.2
通讯作者：
Junmin Zhang
中科院分区：
文献类型：
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作者：
Chaohua Tang;Shuang Li;Kai Zhang;Yunsheng Han;Qingyu Zhao;Xiaoqing Guo;Yuchang Qin;Jingdong Yin;Junmin Zhang
范围：硒（Se）不平衡与许多心脏疾病密切相关，尽管其体内机制仍不清楚。因此，创建了一个猪模型，以便全面了解膳食硒缺乏的心脏反应。方法和结果：总共 24 头猪被分为两个相等的组，分别饲喂 0.007 mg kg−1Se 或 0.3 mg kg−1Se 的饲料，持续 16 周。硒缺乏通过阻断谷胱甘肽和硫氧还蛋白系统引起心脏氧化应激，并增加含硫氧还蛋白结构域的蛋白质 S-亚硝基化。能量产生紊乱，游离脂肪酸超载，三羧酸循环加强，三种呼吸链蛋白增强 S-亚硝基化。过量的游离脂肪酸会导致二酰甘油、磷脂酰胆碱和磷脂酰乙醇胺的合成增加，其中后两者容易氧化并导致丙二醛增加。此外，增加的棕榈酸可以增强神经酰胺的从头合成和积累。此外，硒缺乏通过细胞质 DNA 传感途径引发炎症，从而激活下游干扰素调节因子 7 和核因子 kappa B。结论：本研究确定了硒缺乏导致的脂质代谢脆弱性和炎症引发途径，这可能为人类氧化还原失衡引起的心脏病治疗提供靶标。
Scope: Selenium (Se) disequilibrium is closely involved in many cardiac diseases, although its in vivo mechanism remains uncertain. Therefore, a pig model is created in order to generate a comprehensive picture of cardiac response to dietary Se deficiency.Methods and Results: A total of 24 pigs are divided into two equal groups, which were fed a diet with either 0.007 mg kg−1Se or 0.3 mg kg−1Se for 16 weeks. Se deficiency causes cardiac oxidative stress by blocking glutathione and thioredoxin systems and increases thioredoxin domain‐containing protein S‐nitrosylation. Energy production is disordered, as free fatty acids are overloaded, the tricarboxylic acid cycle is strengthened, and three respiratory chain proteins enhance S‐nitrosylation. Excess free fatty acids lead to increased synthesis of diacylglycerol, phosphatidylcholine, and phosphatidylethanolamine, where the latter two are vulnerable to oxidation and causes an increase in malondialdehyde. Moreover, increased palmitic acid enhances de novo ceramide synthesis and accumulation. Additionally, Se deficiency initiates inflammation via cytosolic DNA‐sensing pathways, which activates downstream interferon regulatory factor 7 and nuclear factor kappa B.Conclusions: The present study identifies a lipid metabolic vulnerability and inflammation initiation pathway via Se deficiency, which may provide targets for human redox imbalance‐induced cardiac disease treatment.