title: Hepatic metabolite profiles in mice with a suboptimal selenium status.
abstract: Selenium is an essential trace element and mediates its functions via various selenoproteins such as glutathione peroxidases or thioredoxin reductases. A suboptimal selenium supply causes metabolic disturbances and is associated with an increased risk to develop different disorders, including cancer or cardiovascular diseases. This study aimed to assess the impact of a suboptimal selenium status on the hepatic metabolome of male mice analyzed by a targeted liquid chromatography/tandem mass spectrometry and a method based on non-targeted gas chromatography hyphenated with mass spectrometry. Feeding animals a diet with about half of the recommended selenium content supplied as selenomethionine caused liver glutathione peroxidase and thioredoxin reductase activities to decline and lipid peroxidation to increase. Serum T3 thyroid hormone concentration also declined via a reduced hepatic deiodinase activity. Metabolite profiling revealed predominantly changes in cysteine and carbon-1 metabolism as well as in selected lipid subclasses. In particular the concentrations of palmitoylcarnitines and oleoylcarnitines (C18:1 and C16:1) and various phosphatidylcholine species containing saturated fatty acids were elevated. Increased taurine levels suggested an enhanced cysteine flux through the salvage pathway whereas increased homocysteine levels appeared to be a consequence of a massive down-regulation of cystathionine β lyase (cystathionine β synthase) and a reduced flux through the transsulfuration pathway. The findings demonstrate that a suboptimal selenium status causes alterations in lipid and carbon-1 metabolism in mouse liver. These changes may contribute to the development of diseases associated with a suboptimal selenium status.
authors.affiliation: ZIEL Research Center of Nutrition and Food Sciences, Department of Biochemistry, Technical University of Munich, Gregor-Mendel-Strasse 2, 85350 Freising, Germany. Electronic address: kersting@tum.de.
authors.forename: Kerstin E
authors.initials: KE
authors.lastname: Geillinger
authors.affiliation: Institute of Experimental Endocrinology, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rathmann
authors.affiliation: Institute of Experimental Endocrinology, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Köhrle
authors.affiliation: ZIEL Research Center of Nutrition and Food Sciences, Department of Biochemistry, Technical University of Munich, Gregor-Mendel-Strasse 2, 85350 Freising, Germany.
authors.forename: Jarlei
authors.initials: J
authors.lastname: Fiamoncini
authors.affiliation: ZIEL Research Center of Nutrition and Food Sciences, Department of Biochemistry, Technical University of Munich, Gregor-Mendel-Strasse 2, 85350 Freising, Germany.
authors.forename: Hannelore
authors.initials: H
authors.lastname: Daniel
authors.affiliation: Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
authors.forename: Anna P
authors.initials: AP
authors.lastname: Kipp
mesh_terms: D000818:Animals; D002331:Carnitine / Q000031:analogs & derivatives / Q000378:metabolism; D002853:Chromatography, Liquid; D008401:Gas Chromatography-Mass Spectrometry; D006003:Glycogen / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012643:Selenium / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D014284:Triiodothyronine / Q000378:metabolism
chemical_list: D008563:Membrane Lipids; C116917:acylcarnitine; D014284:Triiodothyronine; D006003:Glycogen; D012643:Selenium; D002331:Carnitine
keywords: GC-MS; Homocysteine; Liver; Phospholipids; Selenium; Taurine