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Title: Regulation of cardiometabolic risk factors by dietary Toll-like receptor stimulants
Author: Faraj, Tola Abdulsattar
ISNI:       0000 0004 6424 9112
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2017
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Atherosclerosis is a chronic inflammatory disease of the arteries, although the causative agents for inducing inflammatory processes related to atherosclerosis remain unclear. Dietary patterns may play a role in the commencement of inflammation, which may contribute to the progression of the disease. This PhD project aimed to investigate potential mechanisms by which processed foods may induce inflammatory responses (in vitro, ex vivo and in vivo) and may increase cardiometabolic risk factors, with an emphasis on the potential roles of Toll-like receptor (TLR)-2 and TLR4 signaling. The present findings establish that TLR2 and TLR4 stimulants present in food are critical mediators of the capacity of food extracts to induce inflammatory signaling in human primary monocytes. Also, chronic dietary PAMP intake in healthy volunteers revealed that a low PAMP diet decreases cardiometabolic markers (leukocyte count, body weight, abdominal circumference, LDL-C level, thrombocyte counts and plasma leptin concentrations) significantly and these effects are rapidly reversed by a high PAMP diet. In addition, murine studies suggested that Kupffer cells, rather than hepatocytes, are the main sensors of dietary TLR2- and TLR4-stimulants, and that IL-1β signaling plays a key role in the expression of the APR and metabolic phenotypes induced by ingested lipopolysaccharide (LPS) in mice. Moreover, food additives may have an adverse role in changing gut barrier function which may results in the increased translocation of dietary TLR-stimulants into the circulation. In conclusion, these findings suggest that dietary TLR2- and TLR4-stimulants may be considered as a new possible risk factor for coronary artery disease. For the prevention of atherosclerosis, novel therapies could be developed to target the mechanisms of cross-talk between the TLR2/4 receptors, inflammatory responses and lipid regulatory pathways recognised by the current project.
Supervisor: Erridge, Clett ; Herbert, Karl ; Stover, Cordula Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available