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 wellestablished 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 tissuespecific 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.

The interplay of maternal and offspring obesogenic diets: the impact on offspring metabolism and muscle mitochondria in an outbred mouse model

“…While mitochondrial dysfunction is considered a key factor in the pathogenesis of metabolic diseases (Saris and Heymsfield, 2007;Sergi et al, 2019), mitochondria are also essential in intergenerational programming and the transmission of environmental effects to the next generations (Alhassen et al, 2021). Maternal obesity is directly linked with mitochondrial alterations, leading to placental dysfunction, modulating fetal growth and development (Sobrevia et al, 2020;Diniz et al, 2023), with gestational obesity directly affecting the offspring muscle metabolism (Walter and Klaus, 2014;Ampong et al, 2022). Previous research in inbred C57BL/6 mice suggested that ultrastructural aberrations in oocyte mitochondria induced by a maternal OB diet are transferred to the subsequent embryos.…”