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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. 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.

SUBMITTER: Caesar R

PROVIDER: S-EPMC3505865 | biostudies-other | 2012 Dec

REPOSITORIES: biostudies-other

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

Caesar Robert R Reigstad Christopher S CS Bäckhed Helene Kling HK Reinhardt Christoph C Ketonen Maria M Lundén Gunnel Östergren GÖ Cani Patrice D PD Bäckhed Fredrik F

Gut 20120425 12

<h4>Background</h4>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,<h4>Objective</h4>To investigate whether the gut microbiota and, specifically, gut-derived lipopolysaccharide (LPS) promote WAT inflammation and contribute to impaired glucose metabolism.<h4>Method</h4>Macrophage composition and expression of pro ...[more]

PMID: 22535377

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Project description:BackgroundAround 308 million people worldwide are estimated to have impaired glucose tolerance (IGT); 25% to 75% of these will develop diabetes within a decade of initial diagnosis. At diagnosis, half will have tissue-related damage and all have an increased risk for coronary heart disease.ObjectivesThe objective of this review was to assess the effects and safety of Chinese herbal medicines for the treatment of people with impaired glucose tolerance or impaired fasting glucose (IFG).Search strategyWe searched the following databases: The Cochrane Library, PubMed, EMBASE, AMED, a range of Chinese language databases, SIGLE and databases of ongoing trials.Selection criteriaRandomised clinical trials comparing Chinese herbal medicines with placebo, no treatment, pharmacological or non-pharmacological interventions in people with IGT or IFG were considered.Data collection and analysisTwo authors independently extracted data. Trials were assessed for risk of bias against key criteria: random sequence generation, allocation concealment, blinding of participants, outcome assessors and intervention providers, incomplete outcome data, selective outcome reporting and other sources of bias.Main resultsThis review examined 16 trials lasting four weeks to two years involving 1391 participants receiving 15 different Chinese herbal medicines in eight different comparisons. No trial reported on mortality, morbidity or costs. No serious adverse events like severe hypoglycaemia were observed. Meta-analysis of eight trials showed that those receiving Chinese herbal medicines combined with lifestyle modification were more than twice as likely to have their fasting plasma glucose levels return to normal levels (i.e. fasting plasma glucose <7.8 mmol/L and 2hr blood glucose <11.1 mmol/L) compared to lifestyle modification alone (RR 2.07; 95% confidence intervall (CI) 1.52 to 2.82). Those receiving Chinese herbs were less likely to progress to diabetes over the duration of the trial (RR 0.33; 95% CI 0.19 to 0.58). However, all trials had a considerable risk of bias and none of the specific herbal medicines comparison data was available from more than one study. Moreover, results could have been confounded by rates of natural reversion to normal glucose levels.Authors' conclusionsThe positive evidence in favour of Chinese herbal medicines for the treatment of IGT or IFG is constrained by the following factors: lack of trials that tested the same herbal medicine, lack of details on co-interventions, unclear methods of randomisation, poor reporting and other risks of bias.

Dataset Information

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

Publications

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

Similar Datasets

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