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Samad M, Ulfenborg B, Soleimani Sani S, Bauzá Thorbrügge M, Mohan Shrestha M, Ohlsson C, Maliqueo M, Stener-Victorin E, Wernstedt Asterholm I, Benrick A
FASEB J. 39 (8) e70556 [2025-04-30; online 2025-04-18]
Women with obesity who develop gestational diabetes have lower serum adiponectin throughout pregnancy, suggesting that low levels impair the ability to handle metabolic challenges during pregnancy. The placenta expresses adiponectin receptors, and adiponectin could therefore indirectly affect the developing fetus. Here, we aimed to investigate how elevated maternal and fetal adiponectin 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 before and during pregnancy to induce obesity. Mice were euthanized and dissected on gestational day 18.5. Lipid, glucose, and amino acid tracers were administered to the obese pregnant dams to study nutrient uptake. The effects of elevated adiponectin on fetal liver and placental function were further investigated using global proteomics. A 40%-50% increase in serum adiponectin reduced fetal growth in dams fed a HF/HS diet, but not a normal chow diet. The uptake of glucose, lipid, and amino acid tracer was lower, along with decreased expression of several amino acid transporters in the placenta of APNtg dams on HF/HS diet. This suggests that adiponectin decreases placental transfer of nutrients. Livers of fetuses from APNtg dams showed downregulated lipid and amino acid metabolic pathways possibly reflecting an energy deficit. In conclusion, elevated serum adiponectin in obese dams reduced the placental transfer of nutrients, resulting in fetal growth restriction and altered fetal liver function. Maternal adiponectin levels were the main driver of placenta function. While this could be beneficial for pregnancy-related complications like 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.
Glycoproteomics and MS Proteomics [Service]
PubMed 40249643
DOI 10.1096/fj.202403251RR
Crossref 10.1096/fj.202403251RR