Placental superoxide dismutase 3 mediates benefits of maternal exercise on offspring health

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  • Joji Kusuyama, Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School
  • ,
  • Ana Barbara Alves-Wagner, Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School
  • ,
  • Royce H Conlin, Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School
  • ,
  • Nathan S Makarewicz, Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School
  • ,
  • Brent G Albertson, Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School
  • ,
  • Noah B Prince, Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School
  • ,
  • Shio Kobayashi, Section of Immunobiology, Joslin Diabetes Center, Harvard Medical School, Boston
  • ,
  • Chisayo Kozuka, Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School
  • ,
  • Magnus Møller
  • Mette Bjerre
  • Jens Fuglsang
  • Emily Miele, Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School
  • ,
  • Roeland J W Middelbeek, Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School
  • ,
  • Yang Xiudong, Graduate School of Biomedical Sciences, University of Texas at Houston, Houston
  • ,
  • Yang Xia, Graduate School of Biomedical Sciences, University of Texas at Houston, Houston
  • ,
  • Léa Garneau, Institut du Savoir Montfort, Recherche, Ottawa
  • ,
  • Jayonta Bhattacharjee, School of Human Kinetics, Faculty of Health Science University of Ottawa, Ottawa
  • ,
  • Céline Aguer, Institut du Savoir Montfort, Recherche, Ottawa
  • ,
  • Mary Elizabeth Patti, Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School
  • ,
  • Michael F Hirshman, Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School
  • ,
  • Niels Jessen
  • Toshihisa Hatta, Department of Anatomy, Kanazawa Medical University, Ishikawa
  • ,
  • Per Glud Ovesen
  • Kristi B Adamo, School of Human Kinetics, Faculty of Health Science University of Ottawa, Ottawa
  • ,
  • Eva Nozik-Grayck, Cardiovascular Pulmonary Research Laboratories and Pediatric Critical Care, Department of Pediatrics, University of Colorado Anschutz Medical Center, Aurora
  • ,
  • Laurie J Goodyear, Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School

Poor maternal diet increases the risk of obesity and type 2 diabetes in offspring, adding to the ever-increasing prevalence of these diseases. In contrast, we find that maternal exercise improves the metabolic health of offspring, and here, we demonstrate that this occurs through a vitamin D receptor-mediated increase in placental superoxide dismutase 3 (SOD3) expression and secretion. SOD3 activates an AMPK/TET signaling axis in fetal offspring liver, resulting in DNA demethylation at the promoters of glucose metabolic genes, enhancing liver function, and improving glucose tolerance. In humans, SOD3 is upregulated in serum and placenta from physically active pregnant women. The discovery of maternal exercise-induced cross talk between placenta-derived SOD3 and offspring liver provides a central mechanism for improved offspring metabolic health. These findings may lead to novel therapeutic approaches to limit the transmission of metabolic disease to the next generation.

OriginalsprogEngelsk
TidsskriftCell Metabolism
Vol/bind33
Nummer5
Sider (fra-til)939-956.e8
Antal sider27
ISSN1550-4131
DOI
StatusUdgivet - maj 2021

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