Selenium Deficiency Induces Pathological Cardiac Lipid Metabolic Remodeling and Inflammation

• Published in: Molecular nutrition & food research 2022-03, Vol.66 (6), p.e2100644-n/a
• Main Authors: Tang, Chaohua, Li, Shuang, Zhang, Kai, Li, Jing, Han, Yunsheng, Zhao, Qingyu, Guo, Xiaoqing, Qin, Yuchang, Yin, Jingdong, Zhang, Junmin
• Format: Article
• Language: English
• Subjects: Animals; cardiac dysfunction; Ceramide; Coronary artery disease; Deoxyribonucleic acid; Diet; Diglycerides; DNA; Electron transport; Fatty acids; Fatty Acids, Nonesterified; Glutathione; Heart diseases; Inflammation; Interferon; Interferon regulatory factor; Interferon regulatory factor 7; Lecithin; lipid remodeling; Lipids; Malondialdehyde; Medical treatment; Metabolism; Oxidation; Oxidative Stress; Palmitic acid; Phosphatidylcholine; Phosphatidylethanolamine; Protein S; Proteins; Selenium; selenium deficiency; Swine; Synthesis; Thioredoxin; Thioredoxins; Tricarboxylic acid cycle
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.202100644

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−1 Se or 0.3 mg kg−1 Se 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. Dietary Selenium (Se) deficiency changes cardiac global phenome of pig. Se deficiency elevates cardiac reactive oxygen species (ROS) via selenoprotein down‐regulation and blocks glutathione (GSH) and thioredoxin (TRX) systems. Tricarboxylic acid (TCA) cycle is enhanced, while respiratory chain proteins SH are up‐nitrosylated. Lipotoxicity is observed as free fatty acids, while DAG and ceramides are increased by Se deficiency. Se deficiency initiates inflammation by triggering cytosolic DNA‐sensing pathways.