| Literature DB >> 33770509 |
Joji Kusuyama1, Ana Barbara Alves-Wagner2, Royce H Conlin2, Nathan S Makarewicz2, Brent G Albertson2, Noah B Prince2, Shio Kobayashi3, Chisayo Kozuka4, Magnus Møller5, Mette Bjerre6, Jens Fuglsang5, Emily Miele2, Roeland J W Middelbeek2, Yang Xiudong7, Yang Xia7, Léa Garneau8, Jayonta Bhattacharjee9, Céline Aguer10, Mary Elizabeth Patti2, Michael F Hirshman2, Niels Jessen11, Toshihisa Hatta12, Per Glud Ovesen5, Kristi B Adamo9, Eva Nozik-Grayck13, Laurie J Goodyear14.
Abstract
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.Entities:
Keywords: AMPK; DNA methylation; TET; glucose metabolism; maternal exercise; placenta; pregnancy; superoxide dismutase 3; vitamin D
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Year: 2021 PMID： 33770509 PMCID： PMC8103776 DOI： 10.1016/j.cmet.2021.03.004
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287