Impacts of dietary selenium deficiency on metabolic phenotypes of diet-restricted GPX1-overexpressing mice.
We previously reported a spontaneous development of type 2 diabetes-like phenotypes in glutathione peroxidase-1 (GPX1)-overexpressing (OE) mice. Diet restriction of these mice rescued all their phenotypes, except for hyperinsulinemia and hypersecretion of insulin. This study was to determine whether dietary Se deficiency eliminated these two primary effects of GPX1 overproduction. Forty-seven male OE and wild-type (WT) mice were fed an Se-adequate (0.4 mg Se/kg) or deficient (<0.02 mg Se/kg) diet at 2 to 3 g (full-fed = 5 g) per day from 4 to 12 weeks of age. Although dietary Se deficiency did not rescue the primary phenotypes of the diet-restricted OE mice, it exerted a strong effect (p < 0.05) on mRNA or protein levels (or both) of 14 molecules involved in islet insulin synthesis and secretion and hepatic lipogenesis. Dietary Se deficiency exhibited a hypoinsulinemic trend in OE mice and a strong hypolipidemic effect (p < 0.05) in the liver of WT mice. Hepatic lipogenesis was attenuated in OE compared with WT mice. In conclusion, diet restriction might be too overwhelming to allow a demonstration of a dietary Se-depletion effect on the OE phenotypes. Full-fed animals could offer a better chance to illustrate such effects and the underlying mechanisms.
Pepper
Matthew P
MP
Department of Animal Science, Cornell University, Ithaca, New York 14853, USA.
Vatamaniuk
Marko Z
MZ
Yan
Xi
X
Roneker
Carol A
CA
Lei
Xin Gen
XG
D000818:Animals; D031204:Caloric Restriction; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004032:Diet; D004734:Energy Metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D007515:Islets of Langerhans / Q000502:physiology; D008099:Liver / Q000502:physiology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010641:Phenotype; D012643:Selenium / Q000172:deficiency*; D000094765:Glutathione Peroxidase GPX1
D005979:Glutathione Peroxidase; D012643:Selenium; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse