Postweaning Diet affects Offspring Metabolic Outcomes More than Maternal Diet in Male and Female Mice

Authors: CORKEN, ADAM - University Arkansas For Medical Sciences (UAMS); WAHL, ELIZABETH - Arkansas Children'S Nutrition Research Center (ACNC); SIKES, JAMES - Arkansas Children'S Nutrition Research Center (ACNC); THAKALI, KESHARI - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: Physiological Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/9/2026
Publication Date: 4/20/2026
Citation: Corken, A., Wahl, E., Sikes, J.D., Thakali, K.M. 2026. Postweaning Diet affects Offspring Metabolic Outcomes More than Maternal Diet in Male and Female Mice. Physiological Reports. 14(8): Article e70881. https://doi.org/10.14814/phy2.70881.
DOI: https://doi.org/10.14814/phy2.70881

Interpretive Summary: Obesity is a growing public health concern, and researchers are working to understand why some individuals are more likely to gain excess weight and develop related conditions like diabetes and high blood pressure. One important question is whether a mother’s diet during pregnancy can “program” her child’s long-term health, increasing their risk for obesity and cardiovascular problems later in life. In this study, researchers examined how a high-fat, high-sugar diet in mothers before and during pregnancy and nursing affected their offspring. They tracked body weight, metabolism, and blood vessel function in the offspring and also looked at how the offspring’s own diet and sex influenced these outcomes. The study found that while maternal diet had some expected influence, the offspring’s own diet and biological sex were much stronger factors in determining body composition and metabolic health. Importantly, maternal diet did not appear to significantly affect how blood vessels functioned in the offspring. These findings suggest that although early-life influences matter, an individual’s own lifestyle—particularly diet—plays a larger role in shaping metabolic health and obesity risk. This is encouraging from a public health perspective, as it highlights that healthy eating habits later in life can help offset early risk factors. The study helps refine our understanding of obesity by showing that interventions targeting diet and lifestyle may be especially effective, even for individuals who may have been exposed to less optimal conditions early in development.

Technical Abstract: The pervasiveness of obesity necessitates expanded pursuits to understand mechanistic drivers of the condition. Maternal diet during conception and gestation can program offspring towards excessive weight gain. Furthermore, the association between obesity and hypertension suggests that maternal programming may impact offspring vascular reactivity. We investigated whether a maternal high fat+sucrose diet (HFD) prior and during pregnancy and lactation affected offspring body composition, metabolic parameters, and vascular reactivity. Using C57BLJ/6 mice, male and female offspring from control (low fat/sucrose) and HFD fed mothers were fed either a control or HFD for 14 weeks after weaning. After 14 weeks of postweaning diets, linear mixed effect modeling adjusting for sex and litter revealed that offspring HFD and sex were significant drivers of body composition changes, non-fasting serum insulin, serum leptin, and metabolic measures (respiratory exchange ratio, energy expenditure and food intake). Offspring sex had significant effects on fasting glucose and non-fasting triglycerides. Neither maternal nor offspring diet or sex had significant effects on mesenteric artery contractility in the presence or absence of perivascular adipose fat. In conclusion, in our experimental paradigm, offspring diet and sex effects on body composition and metabolic parameters overshadowed maternal HFD programming in male and female offspring.