title: Advanced Running Performance by Genetic Predisposition in Male Dummerstorf Marathon Mice (DUhTP) Reveals Higher Sterol Regulatory Element-Binding Protein (SREBP) Related mRNA Expression in the Liver and Higher Serum Levels of Progesterone.
abstract: Long-term-selected DUhTP mice represent a non-inbred model for inborn physical high-performance without previous training. Abundance of hepatic mRNA in 70-day male DUhTP and control mice was analyzed using the Affymetrix mouse array 430A 2.0. Differential expression analysis with PLIER corrected data was performed using AltAnalyze. Searching for over-representation in biochemical pathways revealed cholesterol metabolism being most prominently affected in DUhTP compared to unselected control mice. Furthermore, pathway analysis by AltAnalyze plus PathVisio indicated significant induction of glycolysis, fatty acid synthesis and cholesterol biosynthesis in the liver of DUhTP mice versus unselected control mice. In contrast, gluconeogenesis was partially inactivated as judged from the analysis of hepatic mRNA transcript abundance in DUhTP mice. Analysis of mRNA transcripts related to steroid hormone metabolism inferred elevated synthesis of progesterone and reduced levels of sex steroids. Abundance of steroid delta isomerase-5 mRNA (Hsd3b5, FC 4.97) was increased and steroid 17-alpha-monooxygenase mRNA (Cyp17a1, FC -11.6) was massively diminished in the liver of DUhTP mice. Assessment of steroid profiles by LC-MS revealed increased levels of progesterone and decreased levels of sex steroids in serum from DUhTP mice versus controls. Analysis of hepatic mRNA transcript abundance indicates that sterol regulatory element-binding protein-1 (SREBP-1) may play a major role in metabolic pathway activation in the marathon mouse model DUhTP. Thus, results from bioinformatics modeling of hepatic mRNA transcript abundance correlated with direct steroid analysis by mass spectrometry and further indicated functions of SREBP-1 and steroid hormones for endurance performance in DUhTP mice.
authors.affiliation: Institute of Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ohde
authors.affiliation: Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Rostock, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Moeller
authors.affiliation: Institute of Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Brenmoehl
authors.affiliation: Institute of Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Walz
authors.affiliation: Institute of Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
authors.forename: Siriluck
authors.initials: S
authors.lastname: Ponsuksili
authors.affiliation: Institute of Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Schwerin
authors.affiliation: Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Rostock, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Fuellen
authors.affiliation: Institute of Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hoeflich
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis; D056726:Genetic Association Studies; D005943:Gluconeogenesis / Q000502:physiology; D006019:Glycolysis / Q000502:physiology; D008099:Liver / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D011374:Progesterone / Q000097:blood*; D012333:RNA, Messenger / Q000096:biosynthesis*; D012420:Running / Q000502:physiology*; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D013251:Steroid Isomerases / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D012333:RNA, Messenger; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D011374:Progesterone; D002784:Cholesterol; D013254:Steroid 17-alpha-Hydroxylase; D013251:Steroid Isomerases; C022660:steroid delta-isomerase