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

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.

SUBMITTER: Kusuyama J

PROVIDER: S-EPMC8103776 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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

Kusuyama Joji J Alves-Wagner Ana Barbara AB Conlin Royce H RH Makarewicz Nathan S NS Albertson Brent G BG Prince Noah B NB Kobayashi Shio S Kozuka Chisayo C Møller Magnus M Bjerre Mette M Fuglsang Jens J Miele Emily E Middelbeek Roeland J W RJW Xiudong Yang Y Xia Yang Y Garneau Léa L Bhattacharjee Jayonta J Aguer Céline C Patti Mary Elizabeth ME Hirshman Michael F MF Jessen Niels N Hatta Toshihisa T Ovesen Per Glud PG Adamo Kristi B KB Nozik-Grayck Eva E Goodyear Laurie J LJ

Cell metabolism 20210325 5

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 promo ...[more]

PMID: 33770509

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Project description:ObjectiveThe intrauterine environment during pregnancy is a critical factor in the development of obesity, diabetes, and cardiovascular disease in offspring. Maternal exercise prevents the detrimental effects of a maternal high fat diet on the metabolic health in adult offspring, but the effects of maternal exercise on offspring cardiovascular health have not been thoroughly investigated.MethodsTo determine the effects of maternal exercise on offspring cardiovascular health, female mice were fed a chow (C; 21% kcal from fat) or high-fat (H; 60% kcal from fat) diet and further subdivided into sedentary (CS, HS) or wheel exercised (CW, HW) prior to pregnancy and throughout gestation. Offspring were maintained in a sedentary state and chow-fed throughout 52 weeks of age and subjected to serial echocardiography and cardiomyocyte isolation for functional and mechanistic studies.ResultsHigh-fat fed sedentary dams (HS) produced female offspring with reduced ejection fraction (EF) compared to offspring from chow-fed dams (CS), but EF was preserved in offspring from high-fat fed exercised dams (HW) throughout 52 weeks of age. Cardiomyocytes from HW female offspring had increased kinetics, calcium cycling, and respiration compared to CS and HS offspring. HS offspring had increased oxidation of the RyR2 in cardiomyocytes coupled with increased baseline sarcomere length, resulting in RyR2 overactivity, which was negated in female HW offspring.ConclusionsThese data suggest a role for maternal exercise to protect against the detrimental effects of a maternal high-fat diet on female offspring cardiac health. Maternal exercise improved female offspring cardiomyocyte contraction, calcium cycling, respiration, RyR2 oxidation, and RyR2 activity. These data present an important, translatable role for maternal exercise to preserve cardiac health of female offspring and provide insight on mechanisms to prevent the transmission of cardiovascular diseases to subsequent generations.

Dataset Information

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

Publications

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

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