Reprogramming of basic metabolic pathways in microbial sepsis: therapeutic targets at last?

EMBO Mol Med. 2018 Aug;10(8):e8712. doi: 10.15252/emmm.201708712.

Abstract

Sepsis is a highly lethal and urgent unmet medical need. It is the result of a complex interplay of several pathways, including inflammation, immune activation, hypoxia, and metabolic reprogramming. Specifically, the regulation and the impact of the latter have become better understood in which the highly catabolic status during sepsis and its similarity with starvation responses appear to be essential in the poor prognosis in sepsis. It seems logical that new interventions based on the recognition of new therapeutic targets in the key metabolic pathways should be developed and may have a good chance to penetrate to the bedside. In this review, we concentrate on the pathological changes in metabolism, observed during sepsis, and the presumed underlying mechanisms, with a focus on the level of the organism and the interplay between different organ systems.

Keywords: hypoxia; inflammation; interventions; metabolic reprogramming; sepsis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Epigenesis, Genetic
  • Glycolysis
  • Humans
  • Hyperglycemia / metabolism
  • Hypoglycemia / metabolism
  • Hypoxia / metabolism
  • Inflammation / metabolism
  • Ketone Bodies / biosynthesis
  • Lipolysis
  • Metabolic Networks and Pathways
  • Mice
  • Mitochondria / metabolism
  • Peroxisome Proliferator-Activated Receptors / metabolism
  • Rats
  • Sepsis / blood
  • Sepsis / diagnosis
  • Sepsis / genetics
  • Sepsis / metabolism*

Substances

  • Blood Glucose
  • Ketone Bodies
  • Peroxisome Proliferator-Activated Receptors