Selenium Deficiency Induces Pathological Cardiac Lipid Metabolic Remodeling and Inflammation.

Abstract

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. A total of 24 pigs are divided into two equal groups, which were fed a diet with either 0.007mg kg-1 Se or 0.3mg 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 kappaB. 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.