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

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          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.

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          Most cited references29

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          Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage.

          Insulin resistance contributes to the pathophysiology of diabetes and is a hallmark of obesity, metabolic syndrome, and many cardiovascular diseases. Therefore, quantifying insulin sensitivity/resistance in humans and animal models is of great importance for epidemiological studies, clinical and basic science investigations, and eventual use in clinical practice. Direct and indirect methods of varying complexity are currently employed for these purposes. Some methods rely on steady-state analysis of glucose and insulin, whereas others rely on dynamic testing. Each of these methods has distinct advantages and limitations. Thus, optimal choice and employment of a specific method depends on the nature of the studies being performed. Established direct methods for measuring insulin sensitivity in vivo are relatively complex. The hyperinsulinemic euglycemic glucose clamp and the insulin suppression test directly assess insulin-mediated glucose utilization under steady-state conditions that are both labor and time intensive. A slightly less complex indirect method relies on minimal model analysis of a frequently sampled intravenous glucose tolerance test. Finally, simple surrogate indexes for insulin sensitivity/resistance are available (e.g., QUICKI, HOMA, 1/insulin, Matusda index) that are derived from blood insulin and glucose concentrations under fasting conditions (steady state) or after an oral glucose load (dynamic). In particular, the quantitative insulin sensitivity check index (QUICKI) has been validated extensively against the reference standard glucose clamp method. QUICKI is a simple, robust, accurate, reproducible method that appropriately predicts changes in insulin sensitivity after therapeutic interventions as well as the onset of diabetes. In this Frontiers article, we highlight merits, limitations, and appropriate use of current in vivo measures of insulin sensitivity/resistance.
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            Obesity and the human microbiome.

            Ruth E Ley (2010)
            Obesity was once rare, but the last few decades have seen a rapid expansion of the proportion of obese individuals worldwide. Recent work has shown obesity to be associated with a shift in the representation of the dominant phyla of bacteria in the gut, both in humans and animal models. This review summarizes the latest research into the association between microbial ecology and host adiposity, and the mechanisms by which microbes in the gut may mediate host metabolism in the context of obesity. Studies of the effect of excess body fat on the abundances of different bacteria taxa in the gut generally show alterations in the gastrointestinal microbiota, and changes during weight loss. The gastrointestinal microbiota have been shown to impact insulin resistance, inflammation, and adiposity via interactions with epithelial and endocrine cells. Large-scale alterations of the gut microbiota and its microbiome (gene content) are associated with obesity and are responsive to weight loss. Gut microbes can impact host metabolism via signaling pathways in the gut, with effects on inflammation, insulin resistance, and deposition of energy in fat stores. Restoration of the gut microbiota to a healthy state may ameliorate the conditions associated with obesity and help maintain a healthy weight.
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              Gut microbiota fermentation of prebiotics increases satietogenic and incretin gut peptide production with consequences for appetite sensation and glucose response after a meal.

              We have previously shown that gut microbial fermentation of prebiotics promotes satiety and lowers hunger and energy intake in humans. In rodents, these effects are associated with an increase in plasma gut peptide concentrations, which are involved in appetite regulation and glucose homeostasis. Our aim was to examine the effects of prebiotic supplementation on satiety and related hormones during a test meal for human volunteers by using a noninvasive micromethod for blood sampling to measure plasma gut peptide concentrations. This study was a randomized, double-blind, parallel, placebo-controlled trial. A total of 10 healthy adults (5 men and 5 women) were randomly assigned to groups that received either 16 g prebiotics/d or 16 g dextrin maltose/d for 2 wk. Meal tolerance tests were performed in the morning to measure the following: hydrogen breath test, satiety, glucose homeostasis, and related hormone response. We show that the prebiotic treatment increased breath-hydrogen excretion (a marker of gut microbiota fermentation) by approximately 3-fold and lowered hunger rates. Prebiotics increased plasma glucagon-like peptide 1 and peptide YY concentrations, whereas postprandial plasma glucose responses decreased after the standardized meal. The areas under the curve for plasma glucagon-like peptide 1 and breath-hydrogen excretion measured after the meal (0-60 min) were significantly correlated (r = 0.85, P = 0.007). The glucose response was inversely correlated with the breath-hydrogen excretion areas under the curve (0-180 min; r = -0.73, P = 0.02). Prebiotic supplementation was associated with an increase in plasma gut peptide concentrations (glucagon-like peptide 1 and peptide YY), which may contribute in part to changes in appetite sensation and glucose excursion responses after a meal in healthy subjects.
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                Author and article information

                Journal
                Nutr Diabetes
                Nutrition & Diabetes
                Nature Publishing Group
                2044-4052
                January 2012
                23 January 2012
                1 January 2012
                : 2
                : 1
                : e28
                Affiliations
                [1 ]Université catholique de Louvain, Louvain Drug Research Institute, Metabolism and Nutrition Research Group , Brussels, Belgium
                [2 ]University of NAMUR – FUNDP, URBC - NARILIS , Namur, Belgium
                Author notes
                [* ]Université catholique de Louvain, Louvain Drug Research Institute, Metabolism and Nutrition Research Group , Avenue Mounier 73, box B1.73.11, B-1200 Brussels, Belgium. E-mail: nathalie.delzenne@ 123456uclouvain.be
                Article
                nutd201124
                10.1038/nutd.2011.24
                3302144
                23154683
                29ae974e-4388-4ff6-b1d0-cceb111ac55d
                Copyright © 2012 Macmillan Publishers Limited

                This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/

                History
                : 13 December 2011
                : 18 December 2011
                Categories
                Original Article

                Endocrinology & Diabetes
                gastrointestinal peptides,obesity,endotoxemia,high fat diet,arabinoxylan oligosaccharides,prebiotic

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