title: Diet-induced obesity in the selenocysteine lyase knockout mouse.
abstract: OBJECTIVE
  Selenocysteine lyase (Scly) mediates selenocysteine decomposition. It was previously demonstrated that, upon adequate caloric intake (12% kcal fat) and selenium deficiency, disruption of Scly in mice leads to development of metabolic syndrome. In this study, we investigate the effect of a high-fat (45% kcal) selenium-adequate diet in Scly knockout (KO) mice on development of metabolic syndrome. Involvement of selenoproteins in energy metabolism after Scly disruption was also examined in vitro in the murine hepatoma cell line, Hepa1-6, following palmitate treatment.
  
  
  RESULTS
  Scly KO mice were more susceptible to diet-induced obesity than their wild-type counterparts after feeding a high-fat selenium-adequate diet. Scly KO mice had aggravated hyperinsulinemia, hypercholesterolemia, glucose, and insulin intolerance, but unchanged inflammatory cytokines and expression of most selenoproteins, except increased serum selenoprotein P (Sepp1). Scly KO mice also exhibited enhanced hepatic levels of pyruvate and enzymes involved in the regulation of pyruvate cycling, such as pyruvate carboxylase (Pcx) and pyruvate dehydrogenase (Pdh). However, in vitro silencing of Scly in Hepa1-6 cells led to diminished Sepp1 expression, and concomitant palmitate treatment decreased Pdh expression.
  
  
  METHODS
  The role of selenium in lipid metabolism is recognized, but specific selenium-dependent mechanisms leading to obesity are unclear. This study uncovers that Scly has a remarkable effect on obesity and metabolic syndrome development triggered by high-fat exposure, independent of the expression of most selenoproteins.
  
  
  CONCLUSIONS
  Diet-induced obesity in Scly KO mice is aggravated, with effects on pyruvate levels and consequent activation of energy metabolism independent of selenoprotein levels.
authors.affiliation: Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa , Honolulu, Hawaii.
authors.forename: Lucia A
authors.initials: LA
authors.lastname: Seale
authors.affiliation: Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa , Honolulu, Hawaii.
authors.forename: Christy L
authors.initials: CL
authors.lastname: Gilman
authors.affiliation: Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa , Honolulu, Hawaii.
authors.forename: Ann C
authors.initials: AC
authors.lastname: Hashimoto
authors.affiliation: Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa , Honolulu, Hawaii.
authors.forename: Ashley N
authors.initials: AN
authors.lastname: Ogawa-Wong
authors.affiliation: Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa , Honolulu, Hawaii.
authors.forename: Marla J
authors.initials: MJ
authors.lastname: Berry
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D059305:Diet, High-Fat / Q000009:adverse effects*; D004734:Energy Metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D008190:Lyases / Q000235:genetics* / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000201:enzymology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000378:metabolism*; D019308:Palmitic Acid / Q000494:pharmacology; D012643:Selenium / Q000378:metabolism; D051140:Selenoproteins / Q000378:metabolism
chemical_list: D006360:Heat-Shock Proteins; D051140:Selenoproteins; D019308:Palmitic Acid; D008190:Lyases; C034278:selenocysteine lyase; D012643:Selenium