Selenomethionine alleviates chronic heat stress-induced breast muscle injury and poor meat quality in broilers via relieving mitochondrial dysfunction and endoplasmic reticulum stress.

In the present study, the chronic heat stress (CHS) broiler model was developed to investigate the potential protection mechanism of organic selenium (selenomethionine, SeMet) on CHS-induced skeletal muscle growth retardation and poor meat quality. Four hundred Arbor Acres male broilers (680 ± 70 g, 21 d old) were grouped into 5 treatments with 8 replicates of 10 broilers per replicate. Broilers in the control group were raised in a thermoneutral environment (22 ± 2 °C) and fed with a basal diet. The other four treatments were exposed to hyperthermic conditions (33 ± 2 °C, 24 h in each day) and fed on the basal diet supplied with SeMet at 0.0, 0.2, 0.4, and 0.6 mg Se/kg, respectively, for 21 d. Results showed that CHS reduced (P < 0.05) the growth performance, decreased (P < 0.05) the breast muscle weight and impaired the meat quality of breast muscle in broilers. CHS induced protein metabolic disorder in breast muscle, which increased (P < 0.05) the expression of caspase 3, caspase 8, caspase 9 and ubiquitin proteasome system related genes, while decreased the protein expression of P-4EBP1. CHS also decreased the antioxidant capacity and induced mitochondrial stress and endoplasmic reticulum (ER) stress in breast muscle, which increased (P < 0.05) the ROS levels, decreased the concentration of ATP, increased the protein expression of HSP60 and CLPX, and increased (P < 0.05) the expression of ER stress biomarkers. Dietary SeMet supplementation linearly increased (P < 0.05) breast muscle Se concentration and exhibited protective effects via up-regulating the expression of the selenotranscriptome and several key selenoproteins, which increased (P < 0.05) body weight, improved meat quality, enhanced antioxidant capacity and mitigated mitochondrial stress and ER stress. What's more, SeMet suppressed protein degradation and improved protein biosynthesis though inhibiting the caspase and ubiquitin proteasome system and promoting the mTOR-4EBP1 pathway. In conclusion, dietary SeMet supplementation increases the expression of several key selenoproteins, alleviates mitochondrial dysfunction and ER stress, improves protein biosynthesis, suppresses protein degradation, thus increases the body weight and improves meat quality of broilers exposed to CHS.

Hydroxy Selenomethionine Exert Different Protective Effects Against Dietary Oxidative Stress-Induced Inflammatory Responses in Spleen and Thymus of Pigs.

Oxidative stress (OS) is widespread in animal husbandry, which causes edema in immune organs and suppresses immune function of animals. Selenium (Se) is an essential trace element involved in immune regulation and improves animals' immunity. In present study, growing and finishing pigs were used to determine the protective effects of the new organic Se (hydroxy selenomethionine, OH-SeMet) on dietary oxidative stress (DOS) induced inflammatory responses, and the corresponding response of selenotranscriptome in spleen and thymus. Forty castrated male pigs (25.0 ± 3.0 kg) were randomly grouped into 5 dietary treatments (n = 8) and fed on basal diet (formulated with normal corn and normal oils) or oxidized diet (formulated with aged corn and oxidized oils) supplied with 0.0, 0.3, 0.6, or 0.9 mg Se/kg OH-SeMet, after 16 weeks, the corresponding indicators were determined. Results showed that DOS moderately increased the spleen and thymus index, decreased the antioxidant capacity of serum, spleen and thymus, and increased the concentration of serum inflammatory cytokines (IL-6 and TNF-α). The inflammatory response in spleen and thymus under DOS were discrepancies, DOS increased the expression of inflammation-related gene (IFN-ß and TNF-α) in thymus, while exhibited no impact on that of the spleen. Dietary OH-SeMet supplementation exhibited protective effects, which decreased the spleen and thymus index, improved the antioxidant capacity of serum, spleen and thymus, and decreased the serum IL-1ß and IL-6 levels. Se supplementation exhibited limited impact on the inflammation-related genes in spleen, except decreased the mRNA expression of IL-8. On the contrary, Se supplementation showed more impact on that of the thymus, which decreased the mRNA expression of IL-8 and TNF-α, increased the expression of IFN-ß, IL-6, IL-10, and MCP1. In addition, selenotranscriptome responsive to dietary Se levels in spleen and thymus were discrepancies. Se supplementation increased the mRNA expression of  the selenotranscriptome in thymus, while exhibited limited impact on that of in spleen. In conclusion, dietary OH-SeMet supplementation mitigates the DOS-induced immunological stress by increasing the antioxidant capacity and altering the expression of inflammation-related genes and selenotranscriptome in immune organs, and these response in spleen and thymus were discrepancies.

Selenomethionine alleviates environmental heat stress induced hepatic lipid accumulation and glycogen infiltration of broilers via maintaining mitochondrial and endoplasmic reticulum homeostasis.

With the increasing of global mean surface air temperature, heat stress (HS) induced by extreme high temperature has become a key factor restricting the poultry industry. Liver is the main metabolic organ of broilers, HS induces liver damage and metabolic disorders, which impairs the health of broilers and affects food safety. As an essential trace element for animals, selenium (Se) involves in the formation of antioxidant system, and its biological functions are generally mediated by selenoproteins. However, the mechanism of Se against HS induced liver damage and metabolic disorders in broilers is inadequate. Therefore, we developed the chronic heat stress (CHS) broiler model and investigated the potential protection mechanism of organic Se (selenomethionine, SeMet) on CHS induced liver damage and metabolic disorders. In present study, CHS caused liver oxidative damage, and induced hepatic lipid accumulation and glycogen infiltration of broilers, which are accompanied by mitochondrial dysfunction, abnormal mitochondrial tricarboxylic acid (TCA) cycle and endoplasmic reticulum (ER) stress. Dietary SeMet supplementation increased the hepatic Se concentration and exhibited protective effects via promoting the expression of selenotranscriptome and several key selenoproteins (GPX4, TXNRD2, SELENOK, SELENOM, SELENOS, SELENOT, GPX1, DIO1, SELENOH, SELENOU and SELENOW). These key selenoproteins synergistically improved the antioxidant capacity, and mitigated the mitochondrial dysfunction, abnormal mitochondrial TCA cycle and ER stress, thus recovered the hepatic triglyceride and glycogen concentration. What's more, SeMet supplementation suppressed lipid and glycogen biosynthesis and promoted lipid and glycogen breakdown in liver of broilers exposed to CHS though regulating the AMPK signals. Overall, our present study reveals a potential mechanism that Se alleviates environment HS induced liver damage and glycogen and lipid metabolism disorders in broilers, which provides a preventive and/or treatment measure for environment HS-dependent hepatic metabolic disorders in poultry industry.

Different Dietary Sources of Selenium Alleviate Hepatic Lipid Metabolism Disorder of Heat-Stressed Broilers by Relieving Endoplasmic Reticulum Stress.

As global warming continues, the phenomenon of heat stress (HS) in broilers occurs frequently. The alleviating effect of different selenium (Se) sources on HS-induced hepatic lipid metabolism disorders in broilers remains unclear. This study compared the protective effects of four Se sources (sodium selenite; selenium yeast; selenomethionine; nano-Se) on HS-induced hepatic lipid metabolism disorder and the corresponding response of selenotranscriptome in the liver of broilers. The results showed that HS-induced liver injury and hepatic lipid metabolism disorder, which were reflected in the increased activity of serum alanine aminotransferase (ALT), the increased concentration of triacylglycerol (TG) and total cholesterol (TC), the increased activity of acetyl-CoA carboxylase (ACC), diacylglycerol O-acyltransferase (DGAT) and fatty acid synthase (FAS), and the decreased activity of hepatic lipase (HL) in the liver. The hepatic lipid metabolism disorder was accompanied by the increased mRNA expression of lipid synthesis related-genes, the decreased expression of lipidolysis-related genes, and the increased expression of endoplasmic reticulum (ER) stress biomarkers (PERK, IRE1, ATF6, GRP78). The dietary supplementation of four Se sources exhibited similar protective effects. Four Se sources increased liver Se concentration and promoted the expression of selenotranscriptome and several key selenoproteins, enhanced liver antioxidant capacity and alleviated HS-induced ER stress, and thus resisted the hepatic lipid metabolism disorders of broilers exposed to HS. In conclusion, dietary supplementation of four Se sources (0.3 mg/kg) exhibited similar protective effects on HS-induced hepatic lipid metabolism disorders of broilers, and the protective effect is connected to the relieving of ER stress.

Selenoproteins synergistically protect porcine skeletal muscle from oxidative damage via relieving mitochondrial dysfunction and endoplasmic reticulum stress.

BACKGROUND: The skeletal muscle of pigs is vulnerable to oxidative damage, resulting in growth retardation. Selenoproteins are important components of antioxidant systems for animals, which are generally regulated by dietary selenium (Se) level. Here, we developed the dietary oxidative stress (DOS)-inducing pig model to investigate the protective effects of selenoproteins on DOS-induced skeletal muscle growth retardation. RESULTS: Dietary oxidative stress caused porcine skeletal muscle oxidative damage and growth retardation, which is accompanied by mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and protein and lipid metabolism disorders. Supplementation with Se (0.3, 0.6 or 0.9 mg Se/kg) in form of hydroxy selenomethionine (OH-SeMet) linearly increased muscular Se deposition and exhibited protective effects via regulating the expression of selenotranscriptome and key selenoproteins, which was mainly reflected in lower ROS levels and higher antioxidant capacity in skeletal muscle, and the mitigation of mitochondrial dysfunction and ER stress. What's more, selenoproteins inhibited DOS induced protein and lipid degradation and improved protein and lipid biosynthesis via regulating AKT/mTOR/S6K1 and AMPK/SREBP-1 signalling pathways in skeletal muscle. However, several parameters such as the activity of GSH-Px and T-SOD, the protein abundance of JNK2, CLPP, SELENOS and SELENOF did not show dose-dependent changes. Notably, several key selenoproteins such as MSRB1, SELENOW, SELENOM, SELENON and SELENOS play the unique roles during this protection. CONCLUSIONS: Increased expression of selenoproteins by dietary OH-SeMet could synergistically alleviate mitochondrial dysfunction and ER stress, recover protein and lipid biosynthesis, thus alleviate skeletal muscle growth retardation. Our study provides preventive measure for OS-dependent skeletal muscle retardation in livestock husbandry.

Hydroxy Selenomethionine Alleviates Hepatic Lipid Metabolism Disorder of Pigs Induced by Dietary Oxidative Stress via Relieving the Endoplasmic Reticulum Stress.

This study used 40 castrated male pigs to determine the protective effects of a new selenium molecule (hydroxy selenomethionine, OH-SeMet) on dietary oxidative stress (DOS) induced hepatic lipid metabolism disorder, and corresponding response of selenotranscriptome. The pigs were randomly grouped into 5 dietary treatments and fed a basal diet formulated with either normal corn and oils or oxidized diet in which the normal corn and oils were replaced by aged corn and oxidized oils, and supplemented with OH-SeMet at 0.0, 0.3, 0.6 and 0.9 mg Se/kg for a period of 16 weeks (n = 8). The results showed that DOS induced liver damage, increased serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels, decreased serum triacylglycerol (TG) level, suppressed antioxidant capacity in the liver, and changed lipid metabolism enzyme activity, thus causing lipid metabolism disorder in the liver. The DOS-induced lipid metabolism disorder was accompanied with endoplasmic reticulum (ER) stress, changes in lipid metabolism-related genes and selenotranscriptome in the liver. Dietary Se supplementation partially alleviated the negative impact of DOS on the lipid metabolism. These improvements were accompanied by increases in Se concentration, liver index, anti-oxidative capacity, selenotranscriptome especially 11 selenoprotein-encoding genes, and protein abundance of GPX1, GPX4 and SelS in the liver, as well as the decrease in SelF abundance. The Se supplementation also alleviated ER stress, restored liver lipid metabolism enzyme activity, increased the mRNA expression of lipid synthesis-related genes, and decreased the mRNA levels of lipidolysis-related genes. In conclusion, the dietary Se supplementation restored antioxidant capacity and mitigated ER stress induced by DOS, thus resisting hepatic lipid metabolism disorders that are associated with regulation of selenotranscriptome.

Selenium Pretreatment Alleviated LPS-Induced Immunological Stress Via Upregulation of Several Selenoprotein Encoding Genes in Murine RAW264.7 Cells.

This study was conducted to profile selenoprotein encoding genes in mouse RAW264.7 cells upon lipopolysaccharide (LPS) challenge and integrate their roles into immunological regulation in response to selenium (Se) pretreatment. LPS was used to develop immunological stress in macrophages. Cells were pretreated with different levels of Se (0, 0.5, 1.0, 1.5, 2.0 µmol Se/L) for 2 h, followed by LPS (100 ng/mL) stimulation for another 3 h. The mRNA expression of 24 selenoprotein encoding genes and 9 inflammation-related genes were investigated. The results showed that LPS (100 ng/mL) effectively induced immunological stress in RAW264.7 cells with induced inflammation cytokines, IL-6 and TNF-α, mRNA expression, and cellular secretion. LPS increased (P < 0.05) mRNA profiles of 9 inflammation-related genes in cells, while short-time Se pretreatment modestly reversed (P < 0.05) the LPS-induced upregulation of 7 genes (COX-2, ICAM-1, IL-1ß, IL-6, IL-10, iNOS, and MCP-1) and further increased (P < 0.05) expression of IFN-ß and TNF-α in stressed cells. Meanwhile, LPS decreased (P < 0.05) mRNA levels of 18 selenoprotein encoding genes and upregulated mRNA levels of TXNRD1 and TXNRD3 in cells. Se pretreatment recovered (P < 0.05) expression of 3 selenoprotein encoding genes (GPX1, SELENOH, and SELENOW) in a dose-dependent manner and increased (P < 0.05) expression of another 5 selenoprotein encoding genes (SELENOK, SELENOM, SELENOS, SELENOT, and TXNRD2) only at a high level (2.0 µmol Se/L). Taken together, LPS-induced immunological stress in RAW264.7 cells accompanied with the global downregulation of selenoprotein encoding genes and Se pretreatment alleviated immunological stress via upregulation of a subset of selenoprotein encoding genes.