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.
- gnotobiotic mice
- gut microbiota
- metabolic inflammation, inflammation
- E coli
- energy metabolism
- inflammatory diseases
- macrophages, obesity
- colonic microflora
- intestinal permeability
- mucosal immunity
- cardiovascular disease
- intestinal epithelium
- intestinal tract
- lipid metabolism
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Funding This work was supported by the Swedish Research Council, Swedish Foundation for Strategic Research, Swedish Diabetes Foundation, Petrus and Augusta Hedlund Foundation, Torsten and Ragnar Söderbergs Foundations, Novo Nordisk Foundation, TORNADO (FP7-KBBE-222720, http://www.fp7tornado.eu/), AstraZeneca through collaboration with the Sahlgrenska Academy, and a LUA-ALF grant from Västra Götalandsregionen. CSR is the recipient of a postdoctoral fellowship from the Wenner-Gren foundation. PDC is a research associate from the FRS-FNRS (Fonds de la recherche scientifique, Belgium) and is the recipient of grants from the FSR (Fonds Spéciaux de Recherche, UCL) and the FRSM (Fonds de la Recherche Scientifique Médicale).
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.
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