title: High Dietary Selenium Intake Alters Lipid Metabolism and Protein Synthesis in Liver and Muscle of Pigs.
abstract: Prolonged high intakes of dietary selenium have been shown to induce gestational diabetes in rats and hyperinsulinemia in pigs.
  
  
  
  Two experiments were conducted to explore metabolic and molecular mechanisms for the diabetogenic potential of high dietary selenium intakes in pigs.
  
  
  
  In Expt. 1, 16 Yorkshire-Landrace-Hampshire crossbred pigs (3 wk old, body weight = 7.5 ± 0.81 kg, 50% males and 50% females) were fed a corn-soybean meal basal diet supplemented with 0.3 or 1.0 mg Se/kg (as selenium-enriched yeast for 6 wk). In Expt. 2, 12 pigs of the same crossbreed (6 wk old, body weight = 16.0 ± 1.8 kg) were fed a similar basal diet supplemented with 0.3 or 3.0 mg Se/kg for 11 wk. Biochemical and gene and protein expression profiles of lipid and protein metabolism and selenoproteins in plasma, liver, muscle, and adipose tissues were analyzed.
  
  
  
  In Expt. 1, the 1-mg-Se/kg diet did not affect body weight or plasma concentrations of glucose and nonesterified fatty acids. In Expt. 2, the 3-mg-Se/kg diet, compared with the 0.3-mg-Se/kg diet, increased (P < 0.05) concentrations of plasma insulin (0.2 compared with 0.4 ng/mL), liver and adipose lipids (41% to 2.4-fold), and liver and muscle protein (10-14%). In liver, the 3-mg-Se/kg diet upregulated (P < 0.05) the expression, activity, or both of key factors related to gluconeogenesis [phosphoenolpyruvate carboxykinase (PEPCK); 13%], lipogenesis [sterol regulatory element binding protein 1 (SREBP1), acetyl-coenzyme A carboxylase (ACC), and fatty acid synthase (FASN); 46-90%], protein synthesis [insulin receptor (INSR), P70 ribosomal protein S6 kinase (P70), and phosphorylated ribosomal protein S6 (P-S6); 88-105%], energy metabolism [AMP-activated protein kinase (AMPK); up to 2.8-fold], and selenoprotein glutathione peroxidase 3 (GPX3; 1.4-fold) and suppressed (P < 0.05) mRNA levels of lipolysis gene cytochrome P450, family 7, subfamily A, polypeptide 1 (CYP7A1; 88%) and selenoprotein gene selenoprotein W1 (SEPW1; 46%). In muscle, the 3-mg-Se/kg diet exerted no effect on the lipid profiles but enhanced (P < 0.05) expression of P-S6 and mammalian target of rapamycin (mTOR; 42-176%; protein synthesis); selenoprotein P (SELP; 40-fold); and tumor suppressor protein 53 (P53) and peroxisome proliferator-activated receptor γ (PPARG; 52-58%; lipogenesis) and suppressed (P < 0.05) expression of INSR (59%; insulin signaling); selenoprotein S (SELS); deiodinases, iodothyronine, type I (DIO1); and thioredoxin reductase 1 (TXNRD1; 50%; selenoproteins); and ACC1 and FASN (35-51%; lipogenesis).
  
  
  
  Our research showed novel roles, to our best knowledge, and mechanisms of high selenium intakes in regulating the metabolism of protein, along with that of lipid, in a tissue-specific fashion in pigs.
authors.affiliation: Department of Animal Science, Cornell University, Ithaca, NY.
authors.forename: Zeping
authors.identifier: 0000-0001-6157-1542
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Animal Science, Cornell University, Ithaca, NY.
authors.forename: Matthew
authors.initials: M
authors.lastname: Barcus
authors.affiliation: Department of Animal Science, Cornell University, Ithaca, NY.
authors.forename: Jonggun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Animal Science, Cornell University, Ithaca, NY.
authors.forename: Krystal L
authors.initials: KL
authors.lastname: Lum
authors.affiliation: Department of Animal Science, Cornell University, Ithaca, NY.
authors.forename: Courtney
authors.initials: C
authors.lastname: Mills
authors.affiliation: Department of Animal Science, Cornell University, Ithaca, NY xl20@cornell.edu.
authors.forename: Xin Gen
authors.initials: XG
authors.lastname: Lei
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005943:Gluconeogenesis / Q000187:drug effects; D007328:Insulin / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects*; D050155:Lipogenesis / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D012643:Selenium / Q000008:administration & dosage* / Q000097:blood; D013552:Swine; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D012643:Selenium
keywords: AMPK; Se; lipid; protein; selenoprotein