title: Early-life physical activity reverses metabolic and Foxo1 epigenetic misregulation induced by gestational sleep disturbance.
abstract: Sleep disorders are highly prevalent during late pregnancy and can impose adverse effects, such as preeclampsia and diabetes. However, the consequences of sleep fragmentation (SF) on offspring metabolism and epigenomic signatures are unclear. We report that physical activity during early life, but not later, reversed the increased body weight, altered glucose and lipid homeostasis, and increased visceral adipose tissue in offspring of mice subjected to gestational SF (SFo). The reversibility of this phenotype may reflect epigenetic mechanisms induced by SF during gestation. Accordingly, we found that the metabolic master switch Foxo1 was epigenetically misregulated in SFo livers in a temporally regulated fashion. Temporal Foxo1 analysis and its gluconeogenetic targets revealed that the epigenetic abnormalities of Foxo1 precede the metabolic syndrome phenotype. Importantly, regular physical activity early, but not later in life, reversed Foxo1 epigenetic misregulation and altered the metabolic phenotype in gestationally SF-exposed offspring. Thus, we have identified a restricted postnatal period during which lifestyle interventions may reverse the Foxo1 epigenetically mediated risk for metabolic dysfunction later in the life, as induced by gestational sleep disorders.
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, Illinois; and.
authors.forename: Vesco
authors.initials: V
authors.lastname: Mutskov
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, Illinois; and.
authors.forename: Abdelnaby
authors.initials: A
authors.lastname: Khalyfa
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, Illinois; and.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, Illinois; and.
authors.forename: Alba
authors.initials: A
authors.lastname: Carreras
authors.affiliation: Department of Human Genetics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, Illinois.
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Nobrega
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, Illinois; and dgozal@uchicago.edu.
authors.forename: David
authors.initials: D
authors.lastname: Gozal
mesh_terms: D050154:Adiposity; D000367:Age Factors; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D005865:Gestational Age; D050152:Intra-Abdominal Fat / Q000378:metabolism / Q000503:physiopathology; D008019:Life Style; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism* / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012307:Risk Factors; D040242:Risk Reduction Behavior; D012890:Sleep; D012893:Sleep Wake Disorders / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D015430:Weight Gain
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D008055:Lipids
keywords: Foxo1 gene; epigenetics; offspring metabolism effect; physical activity; pregnancy sleep disruption; reverse epigenetic effects