title: Maternal obesity has little effect on the immediate offspring but impacts on the next generation.
abstract: Maternal obesity during pregnancy has been linked to an increased risk of obesity and cardiometabolic disease in the offspring, a phenomenon attributed to developmental programming. Programming effects may be transmissible across generations through both maternal and paternal inheritance, although the mechanisms remain unclear. Using a mouse model, we explored the effects of moderate maternal diet-induced obesity (DIO) on weight gain and glucose-insulin homeostasis in first-generation (F1) and second-generation offspring. DIO was associated with insulin resistance, hyperglycemia and dyslipidemia before pregnancy. Birth weight was reduced in female offspring of DIO mothers (by 6%, P = .039), and DIO offspring were heavier than controls at weaning (males by 47%, females by 27%), however there were no differences in glucose tolerance, plasma lipids, or hepatic gene expression at 6 months. Despite the relative lack of effects in the F1, we found clear fetal growth restriction and persistent metabolic changes in otherwise unmanipulated second-generation offspring with effects on birth weight, insulin levels, and hepatic gene expression that were transmitted through both maternal and paternal lines. This suggests that the consequences of the current dietary obesity epidemic may also have an impact on the descendants of obese individuals, even when the phenotype of the F1 appears largely unaffected.
authors.affiliation: Medical Research Council/University of Edinburgh Centre for Reproductive Health, University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom.
authors.forename: Vicky
authors.initials: V
authors.lastname: King
authors.forename: Rachel S
authors.initials: RS
authors.lastname: Dakin
authors.forename: Lincoln
authors.initials: L
authors.lastname: Liu
authors.forename: Patrick W F
authors.initials: PW
authors.lastname: Hadoke
authors.forename: Brian R
authors.initials: BR
authors.lastname: Walker
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Seckl
authors.forename: Jane E
authors.initials: JE
authors.lastname: Norman
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Drake
mesh_terms: D000818:Animals; D001724:Birth Weight / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000209:etiology / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D018811:Maternal Exposure; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D060888:Real-Time Polymerase Chain Reaction; D014280:Triglycerides / Q000378:metabolism; D015430:Weight Gain
chemical_list: D001786:Blood Glucose; D014280:Triglycerides