Profiling of the circadian metabolome in thioacetamide-induced liver cirrhosis in mice

Abstract

Liver cirrhosis can disturb circadian rhythms, decreasing patient quality of life. Changes in metabolic products in cirrhosis are poorly understood. We evaluated changes in liver metabolism products using a thioacetamide-induced mouse model of liver cirrhosis exhibiting circadian rhythm disturbance. Principal component analysis indicated that the circular progression found in the control group was disrupted in the thioacetamide group, and Jonckheere-Terpstra-Kendall analysis showed an imbalanced pattern of oscillating metabolic products. In addition to changes in serotonin and other vitamin A–related metabolites, differences in metabolic products associated with energetics, redox homeostasis, bile acid production, inflammation, and other processes were identified. Carbohydrate metabolism showed a reduction in metabolic products associated with the tricarboxylic acid cycle, suggesting up-regulation of glycolysis and reduced mitochondrial activity. Lipid metabolism showed an increase in ω-oxidation products, suggesting decreased β-oxidation. Conclusion: These data will be useful for chronotherapy and modulation of circadian rhythms in patients with liver damage. (Hepatology Communications 2017;1:704–718).