Högskolan i Skövde

Women with obesity who develop gestational diabetes have lower serum adiponectin throughout pregnancy, suggesting that lowlevels impair the ability to handle metabolic challenges during pregnancy. The placenta expresses adiponectin receptors, and ad-iponectin could therefore indirectly affect the developing fetus. Here, we aimed to investigate how elevated maternal and fetal ad-iponectin affect placental function, fetal growth, and metabolism during pregnancy in normal-weight and obese mice. Wild-type(wt) and adiponectin-overexpressing (APNtg) mice were fed normal chow or a high fat/high sucrose (HF/HS) diet 8 weeks beforeand during pregnancy to induce obesity. Mice were euthanized and dissected on gestational day 18.5. Lipid, glucose, and aminoacid tracers were administered to the obese pregnant dams to study nutrient uptake. The effects of elevated adiponectin on fetalliver and placental function were further investigated using global proteomics. A 40%–50% increase in serum adiponectin re-duced fetal growth in dams fed a HF/HS diet, but not a normal chow diet. The uptake of glucose, lipid, and amino acid tracer waslower, along with decreased expression of several amino acid transporters in the placenta of APNtg dams on HF/HS diet. Thissuggests that adiponectin decreases placental transfer of nutrients. Livers of fetuses from APNtg dams showed downregulatedlipid and amino acid metabolic pathways possibly reflecting an energy deficit. In conclusion, elevated serum adiponectin in obesedams reduced the placental transfer of nutrients, resulting in fetal growth restriction and altered fetal liver function. Maternaladiponectin levels were the main driver of placenta function. While this could be beneficial for pregnancy-related complicationslike babies born large for their gestation age, our study indicates that adiponectin should be in an optimal concentration range,neither too low nor too high, to prevent these complications.