Dataset Information

Wheat-derived arabinoxylan oligosaccharides with prebiotic effect increase satietogenic gut peptides and reduce metabolic endotoxemia in diet-induced obese mice.

ABSTRACT:

Background

Alterations in the composition of gut microbiota -known as dysbiosis- have been proposed to contribute to the development of obesity, thereby supporting the potential interest of nutrients acting on the gut microbes to produce beneficial effect on host energetic metabolism. Non-digestible fermentable carbohydrates present in cereals may be interesting nutrients able to influence the gut microbiota composition.

Objective and design

The aim of the present study was to test the prebiotic potency of arabinoxylan oligosaccharides (AXOS) prepared from wheat bran in a nutritional model of obesity, associated with a low-grade chronic systemic inflammation. Mice were fed either a control diet or a high fat (HF) diet, or a HF diet supplemented with AXOS during 8 weeks.

Results

AXOS supplementation induced caecal and colon enlargement associated with an important bifidogenic effect. It increased the level of circulating satietogenic peptides produced by the colon (peptide YY and glucagon-like peptide-1), and coherently counteracted HF-induced body weight gain and fat mass development. HF-induced hyperinsulinemia and the Homeostasis Model Assessment of insulin resistance were decreased upon AXOS feeding. In addition, AXOS reduced HF-induced metabolic endotoxemia, macrophage infiltration (mRNA of F4/80) in the adipose tissue and interleukin 6 (IL6) in the plasma. The tight junction proteins (zonula occludens 1 and claudin 3) altered upon HF feeding were upregulated by AXOS treatment suggesting that the lower inflammatory tone was associated with the improvement of gut barrier function.

Conclusion

Together, these findings suggest that specific non-digestible carbohydrates produced from cereals such as AXOS constitute a promising prebiotic nutrient in the control of obesity and related metabolic disorders.

SUBMITTER: Neyrinck AM

PROVIDER: S-EPMC3302144 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Publications

Wheat-derived arabinoxylan oligosaccharides with prebiotic effect increase satietogenic gut peptides and reduce metabolic endotoxemia in diet-induced obese mice.

Neyrinck A M AM Van Hée V F VF Piront N N De Backer F F Toussaint O O Cani P D PD Delzenne N M NM

Nutrition & diabetes 20120123

<h4>Background</h4>Alterations in the composition of gut microbiota -known as dysbiosis- have been proposed to contribute to the development of obesity, thereby supporting the potential interest of nutrients acting on the gut microbes to produce beneficial effect on host energetic metabolism. Non-digestible fermentable carbohydrates present in cereals may be interesting nutrients able to influence the gut microbiota composition.<h4>Objective and design</h4>The aim of the present study was to tes ...[more]

PMID: 23154683

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Project description:BackgroundAlterations in the composition of gut microbiota--known as dysbiosis--has been proposed to contribute to the development of obesity, thereby supporting the potential interest of nutrients targeting the gut with beneficial effect for host adiposity. We test the ability of a specific concentrate of water-extractable high molecular weight arabinoxylans (AX) from wheat to modulate both the gut microbiota and lipid metabolism in high-fat (HF) diet-induced obese mice.Methodology/principal findingsMice were fed either a control diet (CT) or a HF diet, or a HF diet supplemented with AX (10% w/w) during 4 weeks. AX supplementation restored the number of bacteria that were decreased upon HF feeding, i.e. Bacteroides-Prevotella spp. and Roseburia spp. Importantly, AX treatment markedly increased caecal bifidobacteria content, in particular Bifidobacterium animalis lactis. This effect was accompanied by improvement of gut barrier function and by a lower circulating inflammatory marker. Interestingly, rumenic acid (C18:2 c9,t11) was increased in white adipose tissue due to AX treatment, suggesting the influence of gut bacterial metabolism on host tissue. In parallel, AX treatment decreased adipocyte size and HF diet-induced expression of genes mediating differentiation, fatty acid uptake, fatty acid oxidation and inflammation, and decreased a key lipogenic enzyme activity in the subcutaneous adipose tissue. Furthermore, AX treatment significantly decreased HF-induced adiposity, body weight gain, serum and hepatic cholesterol accumulation and insulin resistance. Correlation analysis reveals that Roseburia spp. and Bacteroides/Prevotella levels inversely correlate with these host metabolic parameters.Conclusions/significanceSupplementation of a concentrate of water-extractable high molecular weight AX in the diet counteracted HF-induced gut dysbiosis together with an improvement of obesity and lipid-lowering effects. We postulate that hypocholesterolemic, anti-inflammatory and anti-obesity effects are related to changes in gut microbiota. These data support a role for wheat AX as interesting nutrients with prebiotic properties related to obesity prevention.

Project description:UnlabelledThe colonic microbial metabolism is a key contributor to uremic retention solutes accumulating in patients with CKD, relating to adverse outcomes and insulin resistance. Whether prebiotics can reduce intestinal generation of these microbial metabolites and improve insulin resistance in CKD patients not yet on dialysis remains unknown. We performed a randomized, placebo-controlled, double-blind, cross-over study in 40 patients with eGFR between 15 and 45 ml/min/1.73 m2. Patients were randomized to sequential treatment with prebiotic arabinoxylan oligosaccharides (AXOS) (10 g twice daily) and maltodextrin for 4 weeks, or vice versa, with a 4-week wash-out period between both intervention periods. Serum levels and 24h urinary excretion of p-cresyl sulfate, p-cresyl glucuronide, indoxyl sulfate, trimethylamine N-oxide and phenylacetylglutamine were determined at each time point using liquid chromatography-tandem mass spectrometry. In addition, insulin resistance was estimated by the homeostatic model assessment (HOMA-IR). A total of 39 patients completed the study. We observed no significant effect of AXOS on serum p-cresyl sulfate (P 0.42), p-cresyl glucuronide (P 0.59), indoxyl sulfate (P 0.70) and phenylacetylglutamine (P 0.41) and a small, albeit significant decreasing effect on serum trimethylamine N-oxide (P 0.04). There were neither effect of AXOS on 24h urinary excretion of p-cresyl sulfate (P 0.31), p-cresyl glucuronide (P 0.23), indoxyl sulfate (P 0.87) and phenylacetylglutamine (P 0.43), nor on 24h urinary excretion of trimethylamine N-oxide (P 0.97). In addition, we observed no significant change in HOMA-IR (P 0.93). In conclusion, we could not demonstrate an influence of prebiotic AXOS on microbiota derived uremic retention solutes and insulin resistance in patients with CKD not yet on dialysis. Further study is necessary to elucidate whether prebiotic therapy with other characteristics, higher cumulative exposure or in different patient populations may be of benefit.Trial registrationClinicaltrials.gov NCT02141815.

Project description:ObjectiveAdipose tissue expressed endogenous cystathionine gamma lyase (CSE)/hydrogen sulfide (H2S) system. H2S precursor inhibited catecholamine stimulated lipolysis. Thus, we hypothesized that CSE/H2S system regulates lipolysis which contributed to the pathogenesis of insulin resistance.MethodsWe treated rat adipocyte with DL-propargylglycine (PAG, a CSE inhibitor), L-cysteine (an H2S precursor) plus pyridoxial phosphate (co-enzyme) or the H2S chronic release donor GYY4137, then the glycerol level was assayed for assessing the lipolysis. Then, the effects of PAG and GYY4137 on insulin resistance in high fatty diet (HFD) induced obese mice were investigated.ResultsHere, we found that PAG time-dependently increased basal or isoproterenol stimulated lipolysis. However, L-cysteine plus pyridoxial phosphate or GYY4137 significantly reduced it. PAG increased phosphorylated protein kinase A substrate, perilipin 1 and hormone sensitive lipase, but L-cysteine and GYY4137 decreased the parameters. In HFD induced obese mice, PAG increased adipose basal lipolysis, thus blunted fat mass increase, resulting in lowering insulin resistance evidenced by reduction of fasting glucose, insulin level, HOMA index, oral glucose tolerance test (OGTT) curve area and elevating the insulin tolerance test (ITT) response. GYY4137 inhibited lipolysis in vivo without increasing fat mass, but also ameliorated the insulin resistance in HFD mice.ConclusionThese results implicated that inhibition endogenous CSE/H2S system in adipocytes increased lipolysis by a protein kinase A-perilipin/hormone-sensitive lipase pathway, thus blunted fat mass increase and reduced insulin resistance in obese mice; giving H2S donor decreased lipolysis, also reduced insulin resistance induced by HFD. Our data showed that increase or decrease H2S induced opposite lipolysis, but had the same effect on insulin resistance. The paradoxical regulation may be resulted from different action of H2S on metabolic and endocrine function in adipocyte.

Dataset Information

Wheat-derived arabinoxylan oligosaccharides with prebiotic effect increase satietogenic gut peptides and reduce metabolic endotoxemia in diet-induced obese mice.

Background

Objective and design

Results

Conclusion

Publications

Wheat-derived arabinoxylan oligosaccharides with prebiotic effect increase satietogenic gut peptides and reduce metabolic endotoxemia in diet-induced obese mice.

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