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      Gut Microbiota, Microinflammation, Metabolic Profile, and Zonulin Concentration in Obese and Normal Weight Subjects

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          Abstract

          The association between gut microbiota and circulating zonulin level, a marker of intestinal permeability, has not been studied yet. The aim of the study is the assessment of plasma zonulin, haptoglobin and proinflammatory cytokines (TNF- α and IL-6) levels in relation to composition of gut microbiota in obese and normal weight subjects. Circulating inflammation markers, such as TNF- α , sTNFR1, sTNFR2, IL-6, zonulin, and haptoglobin levels were measured and semiquantitative analysis of gut microbiota composition was carried out in 50 obese and 30 normal weight subjects without concomitant diseases. Higher circulating zonulin, TNF- α , sTNFR1, sTNFR2, and IL-6 levels were found in the obese subjects. Plasma zonulin level correlated positively with age ( r = 0.43, P < 0.001), body mass ( r = 0.30, P < 0.01), BMI ( r = 0.33, P < 0.01), fat mass and fat percentage ( r = 0.31, P < 0.01 and r = 0.23, P < 0.05, resp.). Positive correlations between bacterial colony count and sTNFR1 ( r = 0.33, P < 0.01) and plasma zonulin ( r = 0.26, P < 0.05) but not haptoglobin levels were found. Additionally, plasma zonulin level was proportional to daily energy intake ( r = 0.27, P < 0.05) and serum glucose concentration ( r = 0.18, P < 0.05) and inversely proportional to diet protein percentage ( r = −0.23, P < 0.05). Gut microbiota-related systemic microinflammation in the obese is reflected by circulating zonulin level, a potential marker of interstitial permeability.

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          Energy intake is associated with endotoxemia in apparently healthy men.

          The bridge between food intake and weight is not fully understood. Recently, the role of gut microbiota and bacterial lipopolysacharides (LPS) in weight has been noted. The objective was to evaluate the relation between plasma LPS concentration and food intake. A dietary survey was conducted in 1015 subjects randomly recruited in France. The participants were given oral and written instructions on how to keep a consecutive 3-d food record. Plasma LPS was measured in a subsample of 201 men. To assess, under controlled conditions, the differential impact of various high-energy diets, plasma LPS concentrations were measured in mice fed a high-fat or a high-carbohydrate diet over a 4-wk period. In humans, no significant relation was observed between cardiovascular disease risk factors, carbohydrate and protein intakes, and plasma LPS concentration. Conversely, positive correlations were observed with fat and energy intakes. In a multivariate analysis, endotoxemia was independently associated with energy intake. Compared with the control mice, mice fed a high-energy diet showed an increase in plasma LPS. However, in mice fed a high-carbohydrate diet, the increase in plasma LPS was blunted compared with mice fed a high-fat diet. In this large sample of healthy men from a population-based sample, we found a link between food intake and plasma LPS. Experimental data suggest that fat was more efficient in transporting bacterial LPS from the gut lumen into the bloodstream. The results of this study add to the knowledge of mechanisms responsible for relations between food intake and metabolic diseases.
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            Haptoglobin, inflammation and disease.

            Haptoglobin is an acute phase protein that scavenges haemoglobin in the event of intravascular or extravascular haemolysis. The protein exists in humans as three main phenotypes, Hp1-1, Hp2-2 and Hp2-1. Accumulated data on the protein's function has established its strong association with diseases that have inflammatory causes. These include parasitic (malaria), infectious (HIV, tuberculosis) and non-infectious diseases (diabetes, cardiovascular disease and obesity) among others. Phenotype-dependent poor disease outcomes have been linked with the Hp2-2 phenotype. The present review brings this association into perspective by looking at the functions of the protein and how defects in these functions associated with the Hp2 allele affect disease outcome. A model is provided to explain the mechanism, which appears to be largely immunomodulatory.
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              Interaction between colonic acetate and propionate in humans.

              Animal studies suggest that propionate, derived from colonic carbohydrate fermentation, may be gluconeogenic and inhibit cholesterol synthesis in the liver. We therefore studied, in six healthy subjects, the effect of rectally infused solutions containing acetate alone (180 mmol), propionate alone (180 mmol), or a mixture of acetate (180 mmol) and propionate (60 mmol). Relative to the control infusion of normal saline, acetate increased serum cholesterol, glucagon, and acetate concentrations and reduced free fatty acids (FFAs) within 30 min. Propionate alone increased serum propionate, glucose, and glucagon with no effects on cholesterol and a delayed fall in FFAs. The addition of propionate to acetate resulted in no significant rise in serum cholesterol. These results are consistent with the hypothesis that colonic propionate is a gluconeogenic substrate in humans and inhibits the utilization of acetate for cholesterol synthesis.
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                Author and article information

                Journal
                Int J Endocrinol
                Int J Endocrinol
                IJE
                International Journal of Endocrinology
                Hindawi Publishing Corporation
                1687-8337
                1687-8345
                2013
                18 July 2013
                : 2013
                : 674106
                Affiliations
                1Pathophysiology Unit, Department of Pathophysiology, Medical University of Silesia, University of Silesia, 18 Medyków Street, 40-752 Katowice, Poland
                2Health Promotion and Obesity Management Unit, Department of Pathophysiology, Medical University of Silesia, University of Silesia, 18 Medyków Street, 40-752 Katowice, Poland
                3Department of Medical Microbiology, Medical University of Silesia, University of Silesia, 18 Medyków Street, 40-752 Katowice, Poland
                Author notes

                Academic Editor: Malgorzata Kotula-Balak

                Article
                10.1155/2013/674106
                3732644
                23970898
                d9e1abac-3987-46ee-8fbe-26ca1bbb1699
                Copyright © 2013 Agnieszka Żak-Gołąb et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 3 April 2013
                : 22 May 2013
                : 12 June 2013
                Categories
                Research Article

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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