The impact of physiological stress on lipid metabolism, the metabolome, and systemic responses was examined in chickens. To incite a stress response, birds were continuously administered corticosterone (CORT) in their drinking water at three doses (0 mg/L, 10 mg/L, and 30 mg/L), and they were sampled 1, 5, and 12 days after commencement of CORT administration. Corticosterone administration to birds differentially regulated lipogenesis genes (i.e. FAS, ACC, ME, and SREBF1), and histopathological examination indicated lipid deposition in hepatocytes. In addition, CORT affected water-soluble metabolite profiles in the liver, as well as in kidney tissue and breast muscle; thirteen unique metabolites were distinguished in CORT-treated birds and this was consistent with the dysregulation of lipid metabolism due to physiological stress. Acute phase responses (APRs) were also altered by CORT, and in particular, expression of SAA1 was decreased and expression of CP was increased. Furthermore, CORT administration caused lymphoid depletion in the bursa of Fabricius and elevated IL6 and TGFβ2 mRNA expression after 5 and 12 days of CORT administration. Collectively, incitement of physiological stress via administration of CORT in chickens modulated host metabolism and systemic responses, which indicated that energy potentials are diverted from muscle anabolism during periods of stress.

Prenatal stress is known to epigenetically program offspring physiology and behaviour, and may become a risk factor for adult complex diseases. To gain insight into the underlying environment-gene interactions, we used proton nuclear magnetic resonance spectroscopy to analyze urinary metabolomes of male and female adolescents who were in utero during the 1998 Quebec Ice Storm. Metabolomic profiles in adolescent groups were found to be significantly different. Higher prenatal stress exposure generated alterations in metabolic pathways involved in energy metabolism and protein biosynthesis, such as branched-chain amino acid synthesis, alanine metabolism, and ketone body metabolism. Dysregulation of energy and protein metabolism suggests an increased risk of metabolic diseases like insulin resistance, diabetes, and obesity. These findings are consistent with prior observations of physiological phenotypes from this cohort. Understanding the impact of natural disasters on health risks will provide new and improved therapeutic strategies to mitigate stress-associated adverse health outcomes. Using metabolomic biomarkers may also assist in the prediction and prevention of these adverse outcomes.

Stress is one of the most critical determinants of lifetime health and increases the risk of chronic non-communicable diseases. To gain insight into underlying environment-gene interactions, we analyzed the cardiorenal metabolome of adult mice exposed to multidimensional early-life transportation stress. Using proton nuclear magnetic resonance (¹H NMR) spectroscopy, we show that early life stress permanently programs metabolic pathways in somatic organs linked to cardiorenal and mental health disorders in later life. Heart and kidneys of stressed mice revealed robust metabolic markers linked to abnormal energy metabolism, branched-chain amino acid biosynthesis and degradation, methylhistidine metabolism, arginine and proline metabolism, glycine and serine metabolism, and aminoacyl-tRNA biosynthesis. These markers were strongly associated with anxiety-like behaviours. Dysregulation of energy and protein metabolism suggests an increased risk of metabolic diseases like insulin resistance, cardiorenal syndrome, diabetes, and obesity. These findings provide novel insights into the direct effects of early life stress on cardiorenal metabolism and are consistent with prior observations of increased non-communicable disease risk in stressed populations. Thus, stress-associated metabolic signatures in somatic organs may provide early predictors of health risks in later life and reveal new candidates for peripheral biomarker detection with diagnostic value.