| 1. |
- Caesar, Robert, 1973, et al.
(author)
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Gut-derived lipopolysaccharide augments adipose macrophage accumulation but is not essential for impaired glucose or insulin tolerance in mice
- 2012
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In: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 61:12, s. 1701-1707
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Journal article (peer-reviewed)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. 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.
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| 2. |
- Muccioli, Giulio G, et al.
(author)
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The endocannabinoid system links gut microbiota to adipogenesis.
- 2010
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In: Molecular systems biology. - : EMBO. - 1744-4292. ; 6:392
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Journal article (peer-reviewed)abstract
- Obesity is characterised by altered gut microbiota, low-grade inflammation and increased endocannabinoid (eCB) system tone; however, a clear connection between gut microbiota and eCB signalling has yet to be confirmed. Here, we report that gut microbiota modulate the intestinal eCB system tone, which in turn regulates gut permeability and plasma lipopolysaccharide (LPS) levels. The impact of the increased plasma LPS levels and eCB system tone found in obesity on adipose tissue metabolism (e.g. differentiation and lipogenesis) remains unknown. By interfering with the eCB system using CB(1) agonist and antagonist in lean and obese mouse models, we found that the eCB system controls gut permeability and adipogenesis. We also show that LPS acts as a master switch to control adipose tissue metabolism both in vivo and ex vivo by blocking cannabinoid-driven adipogenesis. These data indicate that gut microbiota determine adipose tissue physiology through LPS-eCB system regulatory loops and may have critical functions in adipose tissue plasticity during obesity.
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| 3. |
- Wichmann, Anita, et al.
(author)
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Microbial modulation of energy availability in the colon regulates intestinal transit.
- 2013
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In: Cell host & microbe. - : Elsevier BV. - 1934-6069 .- 1931-3128. ; 14:5, s. 582-90
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Journal article (peer-reviewed)abstract
- Gut microbiota contribute to host metabolic efficiency by increasing energy availability through thefermentation of dietary fiber and production of short-chain fatty acids (SCFAs) in the colon. SCFAs are proposed to stimulate secretion of the proglucagon (Gcg)-derived incretin hormone GLP-1, whichstimulates insulin secretion (incretin response) andinhibits gastric emptying. We find that germ-free(GF) and antibiotic-treated mice, which have severely reduced SCFA levels, have increased basal GLP-1 levels in the plasma and increased Gcg expression in the colon. Increasing energy supply, either through colonization with polysaccharide-fermenting bacteria or through diet, suppressed colonic Gcg expression in GF mice. Increased GLP-1 levels in GF mice did not improve the incretin response but instead slowed intestinal transit. Thus, microbiota regulate the basal levels of GLP-1, and increasing these levels may be an adaptive response to insufficient energy availability in the colon that slows intestinal transit and allows for greater nutrient absorption.
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