Maternal Inactivity Programs Skeletal Muscle Dysfunction in Offspring Mice by Attenuating Apelin Signaling and Mitochondrial Biogenesis
Jun Seok Son,
Song Ah Chae,
Hongyang Wang,
Yanting Chen,
Alejandro Bravo Iniguez,
Jeanene M. de Avila,
Zhihua Jiang,
Mei-Jun Zhu,
Min Du
Affiliations
Jun Seok Son
Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA; School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA
Song Ah Chae
Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA
Hongyang Wang
Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai, China
Yanting Chen
Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA
Alejandro Bravo Iniguez
School of Food Science, Washington State University, Pullman, WA 99164, USA
Jeanene M. de Avila
Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA
Zhihua Jiang
Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA
Mei-Jun Zhu
School of Food Science, Washington State University, Pullman, WA 99164, USA
Min Du
Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA; School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA; Corresponding author
Summary: Although maternal exercise (ME) becomes increasingly uncommon, the effects of ME on offspring muscle metabolic health remain largely undefined. Maternal mice are subject to daily exercise during pregnancy, which enhances mitochondrial biogenesis during fetal muscle development; this is correlated with higher mitochondrial content and oxidative muscle fibers in offspring muscle and improved endurance capacity. Apelin, an exerkine, is elevated due to ME, and maternal apelin administration mirrors the effect of ME on mitochondrial biogenesis in fetal muscle. Importantly, both ME and apelin induce DNA demethylation of the peroxisome proliferator-activated receptor γ coactivator-1α (Ppargc1a) promoter and enhance its expression and mitochondrial biogenesis in fetal muscle. Such changes in DNA methylation were maintained in offspring, with ME offspring muscle expressing higher levels of PGC-1α1/4 isoforms, explaining improved muscle function. In summary, ME enhances DNA demethylation of the Ppargc1a promoter in fetal muscle, which has positive programming effects on the exercise endurance capacity and protects offspring muscle against metabolic dysfunction.
