Obesity-like metabolic signatures in females: from birth to weaning in a mammalian model

Identifying early metabolic signatures and biomarkers is pivotal to understanding the molecular drivers of obesity. This study investigates how genetic variation influences obesity-like metabolic profiles using a mammalian model. Female rabbits from a genetic line selected for growth rate, obtained at two different generations and corresponding to low (LGR) and high (HGR) growth genotypes (GG), were evaluated at first parturition and weaning. Both generations originated from frozen embryos thawed and transferred simultaneously to generate contemporaneous animals. Across 88 animals, we assessed feed intake (n=88) and nutrient digestibility (n=24) and performed untargeted plasma metabolomic profiling (n=48) to characterise systemic metabolic alterations. While no differences were observed in feed intake or digestibility, HGR animals showed significantly elevated plasma levels of Lysophosphatidylethanolamine (0:0/20:4) (LysoPE) at parturition (+131%; P < 0.0001) and weaning (+47%; P < 0.0001) compared to LGR, along with increased betaine at weaning (+16%; P = 0.0189). These findings suggest that genotype-driven metabolic programming may promote nutritional and metabolic adaptations, particularly in membrane remodelling and osmotic stress response. Further targeted studies, including transcriptomic or proteomic integration, are needed to clarify the underlying regulatory pathways and assess possible trade-offs. Ultimately, these insights could advance our understanding of the early metabolic mechanisms contributing to obesity and help to identify biomarkers for early detection and intervention in humans.