Diet-induced obesity in the selenocysteine lyase knockout mouse.

Abstract

AIMS:

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.

INNOVATION:

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.

CONCLUSION:

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: Lucia A Seale, Christy L Gilman, Ann C Hashimoto, Ashley N Ogawa-Wong, Marla J Berry
• Journal: Antioxidants & redox signaling (Antioxid Redox Signal) Vol. 23 Issue 10 Pg. 761-74 (Oct 01 2015) ISSN: 1557-7716 [Electronic] United States
• PMID: 26192035 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Heat-Shock Proteins
• Selenoproteins
• Palmitic Acid
• Lyases
• selenocysteine lyase
• Selenium

Topics

• Animals
• Cell Line, Tumor
• Diet, High-Fat (adverse effects)
• Energy Metabolism
• Heat-Shock Proteins (metabolism)
• Lyases (genetics, metabolism)
• Metabolic Syndrome (enzymology, metabolism)
• Mice, Inbred C57BL
• Mice, Knockout
• Obesity (metabolism)
• Palmitic Acid (pharmacology)
• Selenium (metabolism)
• Selenoproteins (metabolism)