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Maternal exercise conveys protection against NAFLD in the offspring via hepatic metabolic programming.

ABSTRACT: Maternal exercise (ME) during pregnancy has been shown to improve metabolic health in offspring and confers protection against the development of non-alcoholic fatty liver disease (NAFLD). However, its underlying mechanism are still poorly understood, and it remains unclear whether protective effects on hepatic metabolism are already seen in the offspring early life. This study aimed at determining the effects of ME during pregnancy on offspring body composition and development of NAFLD while focusing on proteomic-based analysis of the hepatic energy metabolism during developmental organ programming in early life. Under an obesogenic high-fat diet (HFD), male offspring of exercised C57BL/6J-mouse dams were protected from body weight gain and NAFLD in adulthood (postnatal day (P) 112). This was associated with a significant activation of hepatic AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor alpha (PPARα) and PPAR coactivator-1 alpha (PGC1α) signaling with reduced hepatic lipogenesis and increased hepatic β-oxidation at organ programming peak in early life (P21). Concomitant proteomic analysis revealed a characteristic hepatic expression pattern in offspring as a result of ME with the most prominent impact on Cholesterol 7 alpha-hydroxylase (CYP7A1). Thus, ME may offer protection against offspring HFD-induced NAFLD by shaping hepatic proteomics signature and metabolism in early life. The results highlight the potential of exercise during pregnancy for preventing the early origins of NAFLD.

SUBMITTER: Bae-Gartz I

PROVIDER: S-EPMC7508970 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Maternal exercise conveys protection against NAFLD in the offspring via hepatic metabolic programming.

Bae-Gartz Inga I Kasper Philipp P Großmann Nora N Breuer Saida S Janoschek Ruth R Kretschmer Tobias T Appel Sarah S Schmitz Lisa L Vohlen Christina C Quaas Alexander A Schweiger Michal R MR Grimm Christina C Fischer Axel A Ferrari Nina N Graf Christine C Frese Christian K CK Lang Sonja S Demir Münevver M Schramm Christoph C Fink Gregor G Goeser Tobias T Dötsch Jörg J Hucklenbruch-Rother Eva E

Scientific reports 20200922 1

Maternal exercise (ME) during pregnancy has been shown to improve metabolic health in offspring and confers protection against the development of non-alcoholic fatty liver disease (NAFLD). However, its underlying mechanism are still poorly understood, and it remains unclear whether protective effects on hepatic metabolism are already seen in the offspring early life. This study aimed at determining the effects of ME during pregnancy on offspring body composition and development of NAFLD while fo ...[more]

PMID: 32963289

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Project description:Detrimental exposures in mothers are recognized as risk factors for the development of metabolic dysfunction in offspring. In contrast, maternal exercise has been reported to be an effective strategy to maintain offspring health. However, the mechanisms underlying the protective effects of maternal exercise on adult offspring metabolic homeostasis are largely unclear. This study aims to investigate whether maternal exercise before and during pregnancy could combat the adverse effects of maternal high-fat diet (HFD) on metabolism in 24-week-old male offspring and to explore the role of miRNAs in mediating the effects. Female C57BL/6 mice were fed with either control diet or HFD 3-week prior to breeding and throughout pregnancy and lactation, among whom half of the HFD-fed mice were submitted to voluntary wheel running training 3-week before and during pregnancy. Male offspring were sedentary and fed with a control diet from weaning to 24 weeks. Body weight, the content of inguinal subcutaneous adipose tissue and perirenal visceral adipose tissue, glucose tolerance, and serum insulin and lipids in offspring were analyzed. Hepatic tissues were collected for transcriptome and miRNA sequencing and reverse transcription-quantitative polymerase chain reaction validation. The results showed that maternal HFD resulted in significant glucose intolerance, insulin resistance, and dyslipidemia in adult offspring, which were negated by maternal exercise. Transcriptome sequencing showed that maternal exercise reversed perinatal HFD-regulated genes in adult offspring, which were enriched in glucose and lipid metabolic-related signaling pathways. At the same time, maternal exercise significantly rescued the changes in the expression levels of 3 hepatic miRNAs in adult offspring, and their target genes were involved in the regulation of cholesterol biosynthesis and epigenetic modification, which may play an important role in mediating the intergenerational metabolic regulation of exercise. Overall, our research pioneered the role of miRNAs in mediating the programming effects of maternal exercise on adult offspring metabolism, which might provide novel insight into the prevention and treatment of metabolic disorders in early life.

Dataset Information

Maternal exercise conveys protection against NAFLD in the offspring via hepatic metabolic programming.

Publications

Maternal exercise conveys protection against NAFLD in the offspring via hepatic metabolic programming.

Similar Datasets

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