TY - JOUR
T1 - Maternal Exercise and Paternal Exercise Induce Distinct Metabolite Signatures in Offspring Tissues
AU - Hernández-saavedra, Diego
AU - Markunas, Christina
AU - Takahashi, Hirokazu
AU - Baer, Lisa A.
AU - Harris, Johan E.
AU - Hirshman, Michael F.
AU - Ilkayeva, Olga
AU - Newgard, Christopher B.
AU - Stanford, Kristin I.
AU - Goodyear, Laurie J.
N1 - Acknowledgments. The authors thank Dr. Krithika Ramachandran of the Joslin Diabetes Center for critical review of the manuscript. Funding. This work was supported by National Institutes of Health grants R01-DK101043 (to L.J.G.), R01-DK101043-S1 (L.J.G.), R01-HL138738 (K.I.S.), P30DK124723 (C.B.N.), and 5P30-DK-36836 (Joslin Diabetes Center). H.T. was supported by individual research fellowships from the Uehara Memorial Foundation and Sumitomo Life Welfare Foundation. Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. D.H.-S. analyzed metabolomics data and wrote and edited the manuscript. C.M., L.A.B., and J.E.H. analyzed metabolo-mics data. T.H. performed experiments with isolated hepatocytes. M.F.H. performed in vivo glucose uptake experiments. O.I. performed the metabolomics experiments and helped with the analysis. C.B.N. provided oversight for all metabolomics experiments and wrote and edited the manuscript. K.I.S. designed experiments, performed experiments, analyzed data, and wrote and edited the manuscript. L.J.G. designed experiments, analyzed data, and wrote and edited the manuscript. K.I.S. and L.J.G. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
PY - 2022/10/1
Y1 - 2022/10/1
N2 - That maternal and paternal exercise improve the metabolic health of adult offspring is well established. Tissue and serum metabolites play a fundamental role in the health of an organism, but how parental exercise affects offspring tissue and serum metabolites has not yet been investigated. Here, male and female breeders were fed a high-fat diet and housed with or without running wheels before breeding (males) and before and during gestation (females). Offspring were sedentary and chow fed, with parents as follows: sedentary (Sed), maternal exercise (MatEx), paternal exercise (PatEx), or maternal+paternal exercise (Mat+PatEx). Adult offspring from all parental exercise groups had similar improvement in glucose tolerance and hepatic glucose production. Targeted metabolomics was performed in offspring serum, liver, and triceps muscle. Offspring from MatEx, PatEx, and Mat+PatEx each had a unique tissue metabolite signature, but Mat+PatEx offspring had an additive phenotype relative to MatEx or PatEx alone in a subset of liver and muscle metabolites. Tissue metabolites consistently indicated that the metabolites altered with parental exercise contribute to enhanced fatty acid oxidation. These data identify distinct tissue-specific adaptations and mechanisms for parental exercise-induced improvement in offspring metabolic health. Further mining of this data set could aid the development of novel therapeutic targets to combat metabolic diseases.
AB - That maternal and paternal exercise improve the metabolic health of adult offspring is well established. Tissue and serum metabolites play a fundamental role in the health of an organism, but how parental exercise affects offspring tissue and serum metabolites has not yet been investigated. Here, male and female breeders were fed a high-fat diet and housed with or without running wheels before breeding (males) and before and during gestation (females). Offspring were sedentary and chow fed, with parents as follows: sedentary (Sed), maternal exercise (MatEx), paternal exercise (PatEx), or maternal+paternal exercise (Mat+PatEx). Adult offspring from all parental exercise groups had similar improvement in glucose tolerance and hepatic glucose production. Targeted metabolomics was performed in offspring serum, liver, and triceps muscle. Offspring from MatEx, PatEx, and Mat+PatEx each had a unique tissue metabolite signature, but Mat+PatEx offspring had an additive phenotype relative to MatEx or PatEx alone in a subset of liver and muscle metabolites. Tissue metabolites consistently indicated that the metabolites altered with parental exercise contribute to enhanced fatty acid oxidation. These data identify distinct tissue-specific adaptations and mechanisms for parental exercise-induced improvement in offspring metabolic health. Further mining of this data set could aid the development of novel therapeutic targets to combat metabolic diseases.
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U2 - 10.2337/db22-0341
DO - 10.2337/db22-0341
M3 - Article
C2 - 35838316
SN - 0012-1797
VL - 71
SP - 2094
EP - 2105
JO - Diabetes
JF - Diabetes
IS - 10
ER -