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ABSTRACT: Background
Toll-like receptor 4 (TLR4) contributes to the development of NAFLD (nonalcoholic fatty liver disease) and MetS (metabolic syndrome). It is unclear whether anti-diabetic metformin affects TLR4 expression on blood monocytes, thereby protecting or improving inflammatory parameters. Therefore, we investigated TLR4 in patients with NAFLD meeting different sets of MetS criteria and linked the results with the disease burden.Methods
70 subjects were characterized and divided into three groups: (I) healthy individuals, (II) nonobese with NAFLD and without MetS, and (III) prediabetic, obese with NAFLD and MetS. We determined the concentrations of IL-1?, IL-6, TNF?, and monocyte TLR4 levels in fresh blood as well as in blood cultures with or without metformin supplementation.Results
The characteristics of the study groups revealed a significant association between NAFLD and BMI, MetS and inflammatory parameters, and TLR4. In ex vivo studies, 100 ?M of metformin decreased the TLR4 level by 19.9% (II group) or by 35% (III group) as well as IL-1? and TNF? production. A stepwise multiple regression analysis highlighted a strong effect of metformin on attenuation of the link between TLR4 and NAFLD, and TNF?.Conclusion
We concluded that, by attenuation of the blood monocyte TLR4 level, metformin reduced their inflammatory potential-critical after recruitment these cells into liver. However, this finding should be confirmed after in vivo metformin administration.
SUBMITTER: Zwolak A
PROVIDER: S-EPMC4773077 | biostudies-literature | 2016
REPOSITORIES: biostudies-literature
Zwolak Agnieszka A Słabczyńska Olga O Semeniuk Justyna J Daniluk Jadwiga J Szuster-Ciesielska Agnieszka A
PloS one 20160301 3
<h4>Background</h4>Toll-like receptor 4 (TLR4) contributes to the development of NAFLD (nonalcoholic fatty liver disease) and MetS (metabolic syndrome). It is unclear whether anti-diabetic metformin affects TLR4 expression on blood monocytes, thereby protecting or improving inflammatory parameters. Therefore, we investigated TLR4 in patients with NAFLD meeting different sets of MetS criteria and linked the results with the disease burden.<h4>Methods</h4>70 subjects were characterized and divided ...[more]