title: Gut-derived lipopolysaccharide augments adipose macrophage accumulation but is not essential for impaired glucose or insulin tolerance in mice.
abstract: BACKGROUND
  Obesity is associated with accumulation of macrophages in white adipose tissue (WAT), which contribute to the development of insulin resistance. Germ-free (GF) mice have reduced adiposity and are protected against diet-induced obesity,
  
  
  OBJECTIVE
  To investigate whether the gut microbiota and, specifically, gut-derived lipopolysaccharide (LPS) promote WAT inflammation and contribute to impaired glucose metabolism.
  
  
  METHODS
  Macrophage composition and expression of proinflammatory and anti-inflammatory markers were compared in WAT of GF, conventionally raised and Escherichia coli-monocolonised mice. Additionally, glucose and insulin tolerance in these mice was determined.
  
  
  RESULTS
  The presence of a gut microbiota resulted in impaired glucose metabolism and increased macrophage accumulation and polarisation towards the proinflammatory M1 phenotype in WAT. Monocolonisation of GF mice for 4 weeks with E. coli W3110 or the isogenic strain MLK1067 (which expresses LPS with reduced immunogenicity) resulted in impaired glucose and insulin tolerance and promoted M1 polarisation of CD11b cells in WAT. However, colonisation with E. coli W3110 but not MLK1067 promoted macrophage accumulation and upregulation of proinflammatory and anti-inflammatory gene expression as well as JNK phosphorylation.
  
  
  CONCLUSIONS
  Gut microbiota induced LPS-dependent macrophage accumulation in WAT, whereas impairment of systemic glucose metabolism was not dependent on LPS. These results indicate that macrophage accumulation in WAT does not always correlate with impaired glucose metabolism.
authors.affiliation: Sahlgrenska Center for Cardiovascular and Metabolic Research/Wallenberg Laboratory, Gothenburg, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Caesar
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Reigstad
authors.forename: Helene Kling
authors.initials: HK
authors.lastname: Bäckhed
authors.forename: Christoph
authors.initials: C
authors.lastname: Reinhardt
authors.forename: Maria
authors.initials: M
authors.lastname: Ketonen
authors.forename: Gunnel Östergren
authors.initials: GÖ
authors.lastname: Lundén
authors.forename: Patrice D
authors.initials: PD
authors.lastname: Cani
authors.forename: Fredrik
authors.initials: F
authors.lastname: Bäckhed
mesh_terms: D052436:Adipose Tissue, White / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism*; D005434:Flow Cytometry; D005856:Germ-Free Life; D018149:Glucose Intolerance / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D015151:Immunoblotting; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D007333:Insulin Resistance; D007422:Intestines / Q000382:microbiology*; D008070:Lipopolysaccharides / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D008070:Lipopolysaccharides