Effects of early life adversity on acute metabolic outcomes during neonatal development

Early life adversity has lasting effects on neuroendocrine function and increases risk for psychopathology and metabolic disease. Stress and metabolism are closely intertwined, with critical periods for early life stress overlapping those for metabolic programming. Early life adversity models in rodents have the potential to affect development through multiple pathways, including nutrition, parental behavior, and direct physical stress. In the current study, we investigate how a limited bedding and nesting material (LBN) postnatal environment affects maternal behavior, milk composition, and acute metabolic outcomes in rat offspring. We examined the impact of LBN exposure during two postnatal windows (Early: P0-6 and/or Late: P6-13) and effects of key elements of early experiences (maternal behavior and nutrition) on acute metabolic outcomes, with assessment of sex-specific effects in pups. LBN shifted maternal behavioral phenotype, increased dam milk corticosterone and triglyceride concentration, affected serum metabolic and pituitary hormones in pups, and increased pup estimated daily energy expenditure. Differential gene expression analyses of the liver and arcuate nucleus of the hypothalamus showed timing and sex-specific effects of LBN. LBN predicted expression of genes related to amino acid biosynthesis, protein assembly, and developmental transitions. These effects were associated with individual milk components, pup sex, and pup weight. Collectively, these findings demonstrate that early life adversity alters acute metabolic outcomes through multiple, interacting pathways that may contribute to increased vulnerability to endocrine and metabolic dysfunction later in life.