The Role of Glutamine and Leucine Supplementation in Liver Metabolic Reprogramming During Sepsis

Abstract

Aim: Glutamine (Gln) and leucine (Leu) are amino acids known for modulating various biological functions. This study aimed to identify metabolism-related genes and their transcriptional pattern changes after Gln and/or Leu administration using next-generation sequencing technology in the liver during sepsis, a condition known to lead to liver metabolic reprogramming and damage.Materials and methods: C57BL/6J mice were randomly assigned to a sham control group (C) and four septic groups subjected to cecal ligation and puncture (CLP). The septic groups were as follows: S group, sepsis control with saline injection after CLP; Gln group, injected with Gln after CLP; Leu group, injected with Leu after CLP; and GL group, injected with Gln plus Leu after CLP. All mice were sacrificed on day 4 after the operation, and liver samples were collected for further analysis.Key findings: Gln and/or Leu administration during sepsis significantly altered the hepatic transcriptome with different gene expression patterns. Notably, the G group had the highest number of gene changes among the amino acid-treated groups. Gln administration was associated with more pronounced downregulation of leukocyte inflammatory genes. Carbohydrate metabolic pathways were suppressed, but the oxidative phosphorylation pathway was enhanced by Gln administration, potentially improving metabolic reprogramming during sepsis.Significance: Gln and/or Leu treatment showed promise in alleviating sepsis-induced liver injury; however, only Gln administration alone demonstrated beneficial effects on hepatic macronutrient and energy metabolism during sepsis. These results highlight the potential therapeutic application of specific nutrients for modulating metabolic pathways in response to septic insult.

Note:
Funding declaration: This study was supported by the foundation of National Taiwan University Hospital (112-S0134), Taipei, Taiwan.

Conflict of Interests: The authors declare that they have no conflicts of interests.

Ethical Approval: The protocols were approved by the Institutional Animal Care and Use Committee of Taipei Medical University (LAC-2020-0182).

Keywords: next-generation sequencing technology, metabolic reprogramming, carbohydrate metabolism, Oxidative phosphorylation