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Maternal and Paternal Exercise Induce Distinct Metabolite Signatures in Offspring Tissues

Version 2 2022-08-29, 17:05
Version 1 2022-07-15, 12:18
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posted on 2022-08-29, 17:05 authored by Diego Hernández-Saavedra, Christina Markunas, Hirokazu Takahashi, Lisa A. Baer, Johan E. Harris, Michael F. Hirshman, Olga Ilkayeva, Christopher B. Newgard, Kristin I. Stanford, Laurie J. Goodyear

  

Maternal and paternal exercise are well-established to improve the metabolic health of adult offspring. 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 and had both parents 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 parental exercise were consistent with 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 dataset could aid the development of novel therapeutic targets to combat metabolic diseases.

Funding

This work was supported by National Institutes of Health grants R01-DK101043 (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 Diabetes). H.T. was supported by individual research fellowships from the Uehara Memorial Foundation and Sumitomo Life Welfare Foundation. The authors thanks Dr. Krithika Ramachandran for critical review of the manuscript.

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