title: Resistance to high-fat diet in the female progeny of obese mice fed a control diet during the periconceptual, gestation, and lactation periods.
abstract: With the worldwide epidemic of metabolic syndrome (MetS), the proportion of women that are overweight/obese and overfed during pregnancy has increased. The resulting abnormal uterine environment may have deleterious effects on fetal metabolic programming and lead to MetS in adulthood. A balanced/restricted diet and/or physical exercise often improve metabolic abnormalities in individuals with obesity and type 2 diabetes mellitus (T2D). We investigated whether reducing fat intake during the periconceptual/gestation/lactation period in mothers with high-fat diet (HFD)-induced obesity could be used to modify fetal/neonatal MetS programming positively, thereby preventing MetS. First generation (F1) C57BL/6J female mice with HFD-induced obesity and T2D were crossed with F1 males on control diet (CD). These F1 females were switched to a CD during the periconceptual/gestation/lactation period. At weaning, both male and female second generation (F2) mice were fed a HFD. Weight, caloric intake, lipid parameters, glucose, and insulin sensitivity were assessed. Sensitivity/resistance to the HFD differed significantly between generations and sexes. A similar proportion of the F1 and F2 males (80%) developed hyperphagia, obesity, and T2D. In contrast, a significantly higher proportion of the F2 females (43%) than of the previous F1 generation (17%) were resistant (P<0.01). Despite having free access to the HFD, these female mice were no longer hyperphagic and remained lean, with normal insulin sensitivity and glycemia but mild hypercholesterolemia and glucose intolerance, thus displaying a "satiety phenotype." This suggests that an appropriate dietary fatty acid profile and intake during the periconceptual/gestation/lactation period helps the female offspring to cope with deleterious intrauterine conditions.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Université Paris-Descartes, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Gallou-Kabani
authors.forename: Alexandre
authors.initials: A
authors.lastname: Vigé
authors.forename: Marie-Sylvie
authors.initials: MS
authors.lastname: Gross
authors.forename: Catherine
authors.initials: C
authors.lastname: Boileau
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Rabes
authors.forename: Jamilla
authors.initials: J
authors.lastname: Fruchart-Najib
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Jais
authors.forename: Claudine
authors.initials: C
authors.lastname: Junien
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D018752:Diet, Fat-Restricted; D004041:Dietary Fats / Q000008:administration & dosage* / Q000494:pharmacology; D004198:Disease Susceptibility; D002149:Energy Intake; D005260:Female; D005306:Fertilization; D047109:Fetal Development; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006706:Homeostasis; D006963:Hyperphagia / Q000517:prevention & control; D007328:Insulin / Q000378:metabolism; D007774:Lactation; D050356:Lipid Metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology / Q000503:physiopathology*; D012737:Sex Factors; D015430:Weight Gain
chemical_list: D004041:Dietary Fats; D007328:Insulin; D005947:Glucose