Endogenous hydrocortisone caused metabolic perturbation and nutritional deterioration of animal-derived food in a dose-dependent manner

Endogenous hydrocortisone causes detrimental effects on public health and domestic animal products, but the potential mechanisms remain elusive. Hydrocortisone was detected from seventy-two Guanzhong-Black pigs in three replicates (216 samples) (0.00 ± 46.38 μg kg −1 ), indicating the existence of endogenous hydrocortisone. Herein, we investigated the effects of hydrocortisone on the metabolic signatures in pork via integrative metabolomics and proteomics by UHPLC-Q-Orbitrap HRMS. Animal-derived foods under hydrocortisone-bioaccumulation cause metabolic perturbation by regulating glutamine synthetase expression at the transcriptional level contributed to hydrocortisone-induced toxicity and accelerating the down-regulation of essential amino acids ( l -Histidine 10.74–6.48 mg kg −1 , l -Phenylalanine 3.70–1.57 mg kg −1 ), purine nucleotides (GMP 40.29–5.00 μg kg −1 , etc) that provide nutritional value in a positive feedback loop. Protein-metabolite interactions suggesting that hydrocortisone enhanced nitric oxide synthase and GMP reductase expression (LOQ 3.24–63.39 μg kg −1 ), and affected meat flavor perception, eventually lead to the decline of nutritional value and flesh quality of pork.