The energy homeostasis of offspring exposed in utero to maternal hyperglycemia is modulated in the long term by the composition of breast milk received during lactation. ; L'homéostasie énergétique de la descendance exposée in utero à une hyperglycémie maternelle est modulée à long terme selon la composition du lait maternel reçu pendant la période d'allaitement

International audience ; Gestational diabetes increases the risk of offspring developing type 2 diabetes in adulthood. Epidemiological studies show the benefits of breastfeeding duration on the child's glycemic status, but the long-term effects are still debated. Moreover, preliminary results suggest that milk composition is adapted to maternal hyperglycemia. Thus, in a pre-clinical model, we hypothesize that maternal hyperglycemia could modify milk composition in terms of key regulators of insulin sensitivity, with repercussions on offspring metabolism. Female rats were fed a high-fat, high-sucrose diet (HFHS) or a standard diet (CTL) one week before and during gestation. During lactation, the HFHS group was fed a standard diet (4HFHS) or maintained on HFHS (7HFHS). We calculated the area under the curve (AUC) and an insulin sensitivity index (ISIGutt) following oral glucose tolerance tests (OGTT) performed during gestation (G12) and lactation (L12). Milk composition was characterized on day 1 of lactation (L1), and at L8/L14/L18 by analysis of fatty acid profiles (gas chromatography) and amino acid and ceramide concentrations (liquid chromatography/mass spectrometry). After adoption-crossing, followed by a hypercaloric challenge (D120-J220), the insulin sensitivity of the offspring was studied by OGTT (D60/J210) and euglycemic-hyperinsulinemic clamps (D200).At G12, rats in the HFHS group showed increased insulin and glucose AUCs and a reduced ISIGutt index vs. the CTL group. At L12, glucose AUC was increased and ISIGutt reduced in 7HFHS vs. 4HFHF and CTL rats. Throughout lactation, 7HFHS milk vs. CTL milk showed an increase in insulin-trophic amino acids, and in the ratio of ω6/ω3 polyunsaturated fatty acids, known to stimulate insulin and incretin secretion, but also in certain ceramides. These compositional differences were significant at L1 in 4HFHS milk vs. CTL milk. At D220, male offspring born to HFHS dams and suckled by CTL dams showed an increase in glucose AUC in response to a hypercaloric ...