RRC ID 68915
Author Sekiguchi K, Miyahara H, Inoue M, Kiyota K, Sakai K, Hanada T, Ihara K.
Title Metabolome Characteristics of Liver Autophagy Deficiency under Starvation Conditions in Infancy.
Journal Nutrients
Abstract The liver function is essential for metabolism, detoxification, and bile synthesis, even in the neonatal period. Autophagy plays significance roles in THE adult liver, whereas the role of liver autophagy in the early neonatal period largely remains unclear. To clarify the importance of liver autophagy in the neonatal starvation period, we generated liver-specific autophagy-deficient (Atg5flox/flox; Albumin-Cre) mice and investigated under starvation conditions comparing with control (Atg5flox/+; Albumin-Cre) mice, focusing on serum metabolites and liver histopathology. As a result, autophagy in the liver was found to unessential for the survival under postnatal starvation. A metabolomics analysis of serum metabolites by gas chromatography-tandem mass spectrometry showed a significant difference between the groups, especially after 12-h starvation, suggesting the synergistical adaption of metabolic pathways, such as the "malate-aspartate shuttle", "aspartate metabolism", "urea cycle", and "glycine and serine metabolism". Liver-specific autophagy-deficiency under postnatal starvation conditions can cause a characteristic metabolic alteration suggesting a change of the mitochondrial function. Neonates seemed to maintain ketone production under starvation conditions, even in the autophagy-deficient liver, through a change in the mitochondrial function, which may be an adaptive mechanism for avoiding fatal starvation.
Volume 13(9)
Published 2021-8-29
DOI 10.3390/nu13093026
PII nu13093026
PMID 34578904
PMC PMC8470362
MeSH Animals Animals, Newborn Autophagy* Autophagy-Related Protein 5 / deficiency* Gas Chromatography-Mass Spectrometry Liver / metabolism* Metabolome* Mice Starvation / blood*
IF 4.546
Mice RBRC02975