title: Exercise rescues obese mothers' insulin sensitivity, placental hypoxia and male offspring insulin sensitivity.
abstract: The prevalence of obesity during pregnancy continues to increase at alarming rates. This is concerning as in addition to immediate impacts on maternal wellbeing, obesity during pregnancy has detrimental effects on the long-term health of the offspring through non-genetic mechanisms. A major knowledge gap limiting our capacity to develop intervention strategies is the lack of understanding of the factors in the obese mother that mediate these epigenetic effects on the offspring. We used a mouse model of maternal-diet induced obesity to define predictive correlations between maternal factors and offspring insulin resistance. Maternal hyperinsulinemia (independent of maternal body weight and composition) strongly associated with offspring insulin resistance. To test causality, we implemented an exercise intervention that improved maternal insulin sensitivity without changing maternal body weight or composition. This maternal intervention prevented excess placental lipid deposition and hypoxia (independent of sex) and insulin resistance in male offspring. We conclude that hyperinsulinemia is a key programming factor and therefore an important interventional target during obese pregnancy, and propose moderate exercise as a promising strategy to improve metabolic outcome in both the obese mother and her offspring.
authors.affiliation: University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK.
authors.forename: Denise S
authors.initials: DS
authors.lastname: Fernandez-Twinn
authors.affiliation: Department of Neonatal Medicine, University Hospital of Angers, Angers, France.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Gascoin
authors.affiliation: Department of Physiology, Development &Neuroscience, University of Cambridge, UK.
authors.forename: Barbara
authors.initials: B
authors.lastname: Musial
authors.affiliation: University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Carr
authors.affiliation: University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK.
authors.forename: Daniella
authors.initials: D
authors.lastname: Duque-Guimaraes
authors.affiliation: University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Blackmore
authors.affiliation: University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK.
authors.forename: Maria Z
authors.initials: MZ
authors.lastname: Alfaradhi
authors.affiliation: University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK.
authors.forename: Elena
authors.initials: E
authors.lastname: Loche
authors.affiliation: Department of Physiology, Development &Neuroscience, University of Cambridge, UK.
authors.forename: Amanda N
authors.initials: AN
authors.lastname: Sferruzzi-Perri
authors.affiliation: Department of Physiology, Development &Neuroscience, University of Cambridge, UK.
authors.forename: Abigail L
authors.initials: AL
authors.lastname: Fowden
authors.affiliation: University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Ozanne
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects; D005260:Female; D005951:Glucose Tolerance Test; D006946:Hyperinsulinism / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D009765:Obesity / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D010805:Physical Conditioning, Animal; D010920:Placenta / Q000378:metabolism* / Q000503:physiopathology; D011247:Pregnancy; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D014280:Triglycerides; D002784:Cholesterol