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.
Highlights
Higher endurance performance can be acquired by physical training [1] and further improved by specific diet programs [2]
In Thoroughbred horses, as a large animal model, a genome scan revealed a number of genes relevant for fatty acid metabolism, insulin sensitivity, and muscle strength associated with endurance performance [16]
From a total of 22,690 probe sets present on the Affymetrix 430A Gene Chip 337 probe sets indicated differential mRNA transcript abundance (p < 0.05) with a fold change (FC) > 2 in long-term selected marathon (DUhTP) mice compared to controls (DUC)
Summary
Higher endurance performance can be acquired by physical training [1] and further improved by specific diet programs [2]. The mouse model [12] was selected based on high voluntary running wheel activity in the presence of running wheels during selection. As a consequence, these mice can be used to study interactions of physical activity, home cage activity, and genetic predisposition [14, 15]. Besides effects on muscle structure and function, metabolic adaptations in muscle and adipose tissues may be related to superior running performance in horses [16], and similar observations were made for mice [17] and humans [18]. Physical exercise has been discussed as a means to modulate lipid metabolism as an intervention strategy against fatty liver disease and obesity [19]
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