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Sex-specific effects of exercise ancestry on metabolic, morphological and gene expression phenotypes in multiple generations of mouse offspring.

ABSTRACT: Early life and preconception environmental stimuli can affect adult health-related phenotypes. Exercise training is an environmental stimulus affecting many systems throughout the body and appears to alter offspring phenotypes. The aim of this study was to examine the influence of parental exercise training, or 'exercise ancestry', on morphological and metabolic phenotypes in two generations of mouse offspring. The F0 C57BL/6 mice were exposed to voluntary exercise (EX) or sedentary lifestyle (SED) and bred with like-exposed mates to produce an F1 generation. The F1 mice of both ancestries were sedentary and killed at 8 weeks or bred with littermates to produce an F2 generation, which was also sedentary and killed at 8 weeks. Small but broad generation- and sex-specific effects of exercise ancestry were observed for body mass, fat and muscle mass, serum insulin, glucose tolerance and muscle gene expression. The F1 EX females were lighter than F1 SED females and had lower absolute tibialis anterior and omental fat masses. Serum insulin was higher in F1 EX females compared with F1 SED females. The F2 EX females had impaired glucose tolerance compared with F2 SED females. Analysis of skeletal muscle mRNA levels revealed several generation- and sex-specific differences in mRNA levels for multiple genes, especially those related to metabolic genes (e.g. F1 EX males had lower mRNA levels of Hk2, Ppard, Ppargc1a, Adipoq and Scd1 than F1 SED males). These results provide preliminary evidence that parental exercise training can influence health-related phenotypes in mouse offspring.

SUBMITTER: Guth LM

PROVIDER: S-EPMC3783594 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Sex-specific effects of exercise ancestry on metabolic, morphological and gene expression phenotypes in multiple generations of mouse offspring.

Guth Lisa M LM Ludlow Andrew T AT Witkowski Sarah S Marshall Mallory R MR Lima Laila C J LC Venezia Andrew C AC Xiao Tao T Ting Lee Mei-Ling ML Spangenburg Espen E EE Roth Stephen M SM

Experimental physiology 20130614 10

Early life and preconception environmental stimuli can affect adult health-related phenotypes. Exercise training is an environmental stimulus affecting many systems throughout the body and appears to alter offspring phenotypes. The aim of this study was to examine the influence of parental exercise training, or 'exercise ancestry', on morphological and metabolic phenotypes in two generations of mouse offspring. The F0 C57BL/6 mice were exposed to voluntary exercise (EX) or sedentary lifestyle (S ...[more]

PMID: 23771910

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Project description:Functional assessments of cardiovascular fitness (CVF) are needed to establish animal models of dysfunction, test the effects of novel therapeutics, and establish the cardio-metabolic phenotype of mice. In humans, the graded maximal exercise test (GXT) is a standardized diagnostic for assessing CVF and mortality risk. These tests, which consist of concurrent staged increases in running speed and inclination, provide diagnostic cardio-metabolic parameters, such as, VO2max, anaerobic threshold, and metabolic crossover. Unlike the human-GXT, published mouse treadmill tests have set, not staged, increases in inclination as speed progress until exhaustion (PXT). Additionally, they often lack multiple cardio-metabolic parameters. Here, we developed a mouse-GXT with the intent of improving mouse-exercise testing sensitivity and developing translatable parameters to assess CVF in healthy and dysfunctional mice. The mouse-GXT, like the human-GXT, incorporated staged increases in inclination, speed, and intensity; and, was designed by considering imitations of the PXT and differences between human and mouse physiology. The mouse-GXT and PXTs were both tested in healthy mice (C57BL/6J, FVBN/J) to determine their ability to identify cardio-metabolic parameters (anaerobic threshold, VO2max, metabolic crossover) observed in human-GXTs. Next, theses assays were tested on established diet-induced (obese-C57BL/6J) and genetic (cardiac isoform Casq2-/-) models of cardiovascular dysfunction. Results showed that both tests reported VO2max and provided reproducible data about performance. Only the mouse-GXT reproducibly identified anaerobic threshold, metabolic crossover, and detected impaired CVF in dysfunctional models. Our findings demonstrated that the mouse-GXT is a sensitive, non-invasive, and cost-effective method for assessing CVF in mice. This new test can be used as a functional assessment to determine the cardio-metabolic phenotype of various animal models or the effects of novel therapeutics.

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Dataset Information

Sex-specific effects of exercise ancestry on metabolic, morphological and gene expression phenotypes in multiple generations of mouse offspring.

Publications

Sex-specific effects of exercise ancestry on metabolic, morphological and gene expression phenotypes in multiple generations of mouse offspring.

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