Gut-derived lipopolysaccharide augments adipose macrophage accumulation but is not essential for impaired glucose or insulin tolerance in mice

• Published in: Gut Vol. 61; no. 12; pp. 1701 - 1707
• Main Authors: Caesar, Robert, Reigstad, Christopher S, Bäckhed, Helene Kling, Reinhardt, Christoph, Ketonen, Maria, Östergren Lundén, Gunnel, Cani, Patrice D, Bäckhed, Fredrik
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Society of Gastroenterology 01.12.2012; BMJ Publishing Group; BMJ Publishing Group LTD; BMJ Group
• Subjects: Adipose Tissue, White - immunology; Adipose Tissue, White - metabolism; Adipose Tissue, White - pathology; Animals; Biological and medical sciences; Biomarkers - metabolism; cardiovascular disease; colonic microflora; Diabetes. Impaired glucose tolerance; diet-induced obesity; E coli; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; endotoxemia; Endotoxin; energy metabolism; Escherichia; Escherichia coli - metabolism; escherichia-coli; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Flow Cytometry; Gastroenterologi; Gastroenterology and Hepatology; Gastroenterology. Liver. Pancreas. Abdomen; Germ-Free Life; Glucose; Glucose Intolerance - immunology; Glucose Intolerance - metabolism; Glucose Intolerance - microbiology; Glucose Intolerance - pathology; gnotobiotic mice; gut microbiota; Immunoblotting; Immunohistochemistry; inflammation; Inflammation - immunology; Inflammation - metabolism; Inflammation - microbiology; Inflammation - pathology; inflammatory diseases; innate immunity; Insulin Resistance; intestinal epithelium; intestinal permeability; intestinal tract; Intestines - microbiology; Laboratories; lipid metabolism; Lipopolysaccharides - metabolism; lps; macrophages; Macrophages - metabolism; Male; Medical sciences; Metabolic disorders; metabolic inflammation; Mice; microbiota; modifications; mucosal immunity; Obesity; Original; prebiotic; resistance; Reverse Transcriptase Polymerase Chain Reaction; Rodents; tissue; toll-like receptors; California; Endocrinopathy; Rodentia; Gut; Insulin; Accumulation; Vertebrata; Mammalia; Mouse; Animal; Gastroenterology; Lipopolysaccharide; Impaired glucose tolerance; Macrophage
• ISSN: 0017-5749; 1468-3288
• DOI: 10.1136/gutjnl-2011-301689

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. Method 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. Conclusion 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.