title: Metformin Changes the Relationship between Blood Monocyte Toll-Like Receptor 4 Levels and Nonalcoholic Fatty Liver Disease-Ex Vivo Studies.
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-1β, IL-6, TNFα, 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 μM of metformin decreased the TLR4 level by 19.9% (II group) or by 35% (III group) as well as IL-1β and TNFα production. A stepwise multiple regression analysis highlighted a strong effect of metformin on attenuation of the link between TLR4 and NAFLD, and TNFα.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine and Internal Medicine in Nursing, Medical University, Lublin, Poland.|Department of Endocrinology, Medical University, Lublin, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Zwolak
authors.affiliation: Department of Virology and Immunology, Maria Curie-Skłodowska University, Lublin, Poland.
authors.forename: Olga
authors.initials: O
authors.lastname: Słabczyńska
authors.affiliation: Department of Virology and Immunology, Maria Curie-Skłodowska University, Lublin, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Semeniuk
authors.affiliation: Department of Internal Medicine and Internal Medicine in Nursing, Medical University, Lublin, Poland.|Department of Gastroenterology with the Endoscopic Laboratory, Medical University, Lublin, Poland.
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Daniluk
authors.affiliation: Department of Virology and Immunology, Maria Curie-Skłodowska University, Lublin, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Szuster-Ciesielska
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D007004:Hypoglycemic Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D008687:Metformin