Faraj TF et al Endotoxin metabolism review (Rev2).pdf (472.32 kB)
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Host defences against metabolic endotoxaemia and their impact on lipopolysaccharide detection

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journal contribution
posted on 20.01.2017, 11:35 by Tola A. Faraj, Catherine L. McLaughlin, Clett Erridge
Bacterial endotoxin (lipopolysaccharide, LPS), is one of the most potent inducers of inflammatory signalling, yet it is abundant in the human gut and the modern diet. Small quantities of LPS routinely translocate from the gut lumen to the circulation (so-called ‘metabolic endotoxaemia’), and elevated plasma LPS concentrations are reported in a variety of chronic non-communicable diseases, including obesity, non-alcoholic fatty liver disease, atherosclerosis and type II diabetes. Murine models of experimentally-induced endotoxaemia and Toll-like receptor-4 deficiency suggest that endotoxin may promote the metabolic disturbances that underpin these diseases. However, as bioactive LPS is cleared rapidly from the circulation, and reported levels of endotoxin in human plasma vary widely, the potential relevance of metabolic endotoxaemia to human disease remains unclear. We here review insight into these questions gained from human and murine models of experimental endotoxaemia, focussing on the kinetics of LPS neutralisation and its clearance from blood, the limitations of the widely used limulus assay and alternative methods for LPS quantitation. We conclude that although new methods for LPS measurement will be required to definitively quantify the extent of metabolic endotoxaemia in man, evidence from numerous approaches suggests that this molecule may play a key role in the development of diverse metabolic diseases.

Funding

Tola Faraj is supported by a PhD studentship sponsored by the Higher Committee for Education Development in Iraq (D-11-242).

History

Citation

International Reviews of Immunology, 2017

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Cardiovascular Sciences

Version

AM (Accepted Manuscript)

Published in

International Reviews of Immunology

Publisher

Informa Healthcare

issn

0883-0185

eissn

1563-5244

Acceptance date

06/01/2017

Available date

01/03/2018

Publisher version

http://www.tandfonline.com/doi/full/10.1080/08830185.2017.1280483

Notes

The file associated with this record is under embargo until 12 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.

Language

en