Maternal obesity alters offspring liver and skeletal muscle metabolism in early post-puberty despite maintaining a normal post-weaning dietary lifestyle.

Abstract

Maternal obesity (MO) during pregnancy is linked to increased and premature risk of age-related metabolic diseases in the offspring. However, the underlying molecular mechanisms still remain not fully understood. Using a well-established nonhuman primate model of MO, we analyzed tissue biopsies and plasma samples obtained from post-pubertal offspring (3-6.5 y) of MO mothers (n=19) and from control animals born to mothers fed a standard diet (CON, n=13). All offspring ate a healthy chow diet after weaning. Using untargeted gas chromatography-mass spectrometry metabolomics analysis, we quantified a total of 351 liver, 316 skeletal muscle, and 423 plasma metabolites. We identified 58 metabolites significantly altered in the liver and 46 in the skeletal muscle of MO offspring, with 8 metabolites shared between both tissues. Several metabolites were changed in opposite directions in males and females in both liver and skeletal muscle. Several tissue-specific and 4 shared metabolic pathways were identified from these dysregulated metabolites. Interestingly, none of the tissue-specific metabolic changes were reflected in plasma. Overall, our study describes characteristic metabolic perturbations in the liver and skeletal muscle in MO offspring, indicating that metabolic programming in utero persists postnatally, and revealing potential novel mechanisms that may contribute to age-related metabolic diseases later in life.