title: Toll-like receptor 5 in obesity: the role of gut microbiota and adipose tissue inflammation.
abstract: OBJECTIVE
  This study aimed at establishing bacterial flagellin-recognizing toll-like receptor 5 (TLR5) as a novel link between gut microbiota composition, adipose tissue inflammation, and obesity.
  
  
  METHODS
  An adipose tissue microarray database was used to compare women having the highest (n = 4, H-TLR) and lowest (n = 4, L-TLR) expression levels of TLR5-signaling pathway genes. Gut microbiota composition was profiled using flow cytometry and FISH. Standard laboratory techniques were used to determine anthropometric and clinical variables. In vivo results were verified using cultured human adipocytes.
  
  
  RESULTS
  The H-TLR group had higher flagellated Clostridium cluster XIV abundance and Firmicutes-to-Bacteroides ratio. H-TLR subjects had obese phenotype characterized by greater waist circumference, fat %, and blood pressure (P < 0.05 for all). They also had higher leptin and lower adiponectin levels (P < 0.05 for both). Six hundred and sixty-eight metabolism- and inflammation-related adipose tissue genes were differentially expressed between the groups. In vitro studies confirmed that flagellin activated TLR5 inflammatory pathways, decreased insulin signaling, and increased glycerol secretion.
  
  
  CONCLUSIONS
  The in vivo findings suggest that flagellated Clostridium cluster XIV bacteria contribute to the development of obesity through distorted adipose tissue metabolism and inflammation. The in vitro studies in adipocytes show that the underlying mechanisms of the human findings may be due to flagellin-activated TLR5 signaling.
authors.affiliation: Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland; Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Pekkala
authors.forename: Eveliina
authors.initials: E
authors.lastname: Munukka
authors.forename: Lingjia
authors.initials: L
authors.lastname: Kong
authors.forename: Eija
authors.initials: E
authors.lastname: Pöllänen
authors.forename: Reija
authors.initials: R
authors.lastname: Autio
authors.forename: Christophe
authors.initials: C
authors.lastname: Roos
authors.forename: Petri
authors.initials: P
authors.lastname: Wiklund
authors.forename: Pamela
authors.initials: P
authors.lastname: Fischer-Posovszky
authors.forename: Martin
authors.initials: M
authors.lastname: Wabitsch
authors.forename: Markku
authors.initials: M
authors.lastname: Alen
authors.forename: Pentti
authors.initials: P
authors.lastname: Huovinen
authors.forename: Sulin
authors.initials: S
authors.lastname: Cheng
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003013:Clostridium / Q000502:physiology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007422:Intestines / Q000382:microbiology*; D064307:Microbiota / Q000502:physiology*; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology; D015434:Panniculitis / Q000235:genetics* / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D010641:Phenotype; D015398:Signal Transduction; D051198:Toll-Like Receptor 5 / Q000502:physiology*; D055815:Young Adult
chemical_list: C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5