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      Postprandial Effect of a High-Fat Meal on Endotoxemia in Arab Women with and without Insulin-Resistance-Related Diseases

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          Abstract

          This study determined the effects of a high-fat meal on circulating endotoxin and cardiometabolic indices in adult Arab women. The cohort consisted of 92 consenting Saudi women (18 non-diabetic (ND)) control subjects; Age 24.4 ± 7.9 year; body mass index (BMI) 22.2 ± 2.2 Kg/m 2), 24 overweight/obese (referred to as overweight-plus (overweight +)) subjects (Age 32.0 ± 7.8 year; BMI 28.5 ± 1.5 Kg/m 2) and 50 type 2 diabetes mellitus (T2DM) patients (Age 41.5 ± 6.2 year; BMI 35.2 ± 7.7 Kg/m 2). All were given a high-fat meal (standardized meal: 75 g fat, 5 g carbohydrate, 6 g protein) after an overnight fast of 12–14 h. Anthropometrics were obtained and fasting blood glucose, lipids, and endotoxin were serially measured for four consecutive postprandial hours. Endotoxin levels were significantly elevated prior to a high-fat meal in the overweight + and T2DM than the controls ( p < 0.05). Furthermore, the postprandial cardiometabolic changes led to a more detrimental risk profile in T2DM subjects than other groups, with serial changes most notable in glucose, triglycerides, high density lipoprotein-cholesterol (HDL-cholesterol), and insulin levels ( p-values < 0.05). The same single meal given to subjects with different metabolic states had varying impacts on cardiometabolic health. Endotoxemia is exacerbated by a high-fat meal in Arab subjects with T2DM, accompanied by a parallel increase in cardiometabolic risk profile, suggesting disparity in disease pathogenesis of those with or without T2DM through the altered cardiometabolic risk profile rather than variance in metabolic endotoxinaemia with a high-fat meal.

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          IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance.

          Tumor necrosis factor-alpha (TNF-alpha) is an important mediator of insulin resistance in obesity and diabetes through its ability to decrease the tyrosine kinase activity of the insulin receptor (IR). Treatment of cultured murine adipocytes with TNF-alpha was shown to induce serine phosphorylation of insulin receptor substrate 1 (IRS-1) and convert IRS-1 into an inhibitor of the IR tyrosine kinase activity in vitro. Myeloid 32D cells, which lack endogenous IRS-1, were resistant to TNF-alpha-mediated inhibition of IR signaling, whereas transfected 32D cells that express IRS-1 were very sensitive to this effect of TNF-alpha. An inhibitory form of IRS-1 was observed in muscle and fat tissues from obese rats. These results indicate that TNF-alpha induces insulin resistance through an unexpected action of IRS-1 to attenuate insulin receptor signaling.
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            The indigenous gastrointestinal microflora.

            R. Berg (1996)
            The indigenous gastrointestinal (GI) tract microflora has profound effects on the anatomical, physiological and immunological development of the host. The indigenous microflora stimulates the host immune system to respond more quickly to pathogen challenge and, through bacterial antagonism, inhibits colonization of the GI tract by overt exogenous pathogens. Indigenous GI bacteria are also opportunistic pathogens and can translocate across the mucosal barrier to cause systemic infection in debilitated hosts.
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              Evidence for an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative stress generation: effects of short- and long-term simvastatin treatment.

              Postprandial hypertriglyceridemia and hyperglycemia are considered risk factors for cardiovascular disease. Evidence suggests that postprandial hypertriglyceridemia and hyperglycemia induce endothelial dysfunction through oxidative stress; however, the distinct role of these two factors is a matter of debate. Thirty type 2 diabetic patients and 20 normal subjects ate 3 different meals: a high-fat meal; 75 g glucose alone; and high-fat meal plus glucose. Glycemia, triglyceridemia, nitrotyrosine, and endothelial function were assayed during the tests. Subsequently, diabetics took 40 mg/d simvastatin or placebo for 12 weeks. The 3 tests were performed again at baseline, between 3 to 6 days after the start, and at the end of each study. High-fat load and glucose alone produced a decrease of endothelial function and an increase of nitrotyrosine in normal and diabetic subjects. These effects were more pronounced when high fat and glucose were combined. Short-term simvastatin treatment had no effect on lipid parameters but reduced the effect on endothelial function and nitrotyrosine observed during each different test. Long-term simvastatin treatment was accompanied by a lower increase in postprandial triglycerides, which was followed by smaller variations of endothelial function and nitrotyrosine during the tests. This study shows an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial function, suggesting oxidative stress as common mediator of such effect. Simvastatin shows a beneficial effect on oxidative stress and endothelial dysfunction, which may be ascribed to a direct effect as well as the lipid-lowering action of the drug.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                04 August 2015
                August 2015
                : 7
                : 8
                : 6375-6389
                Affiliations
                [1 ]Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV2 2DX, UK; E-Mails: dara.aldesi@ 123456warwick.ac.uk (D.A.A.-D.); s.l.sabico@ 123456warwick.ac.uk (S.S.); g.tripathi@ 123456warwick.ac.uk (G.T.)
                [2 ]Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11451, Saudi Arabia; E-Mail: malsaif@ 123456ksu.edu.sa
                [3 ]Biomarkers Research Program, Riyadh Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia; E-Mail: nasiruddin2006@ 123456gmail.com
                [4 ]Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
                [5 ]Obesity Research Center, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia; E-Mails: dralfadda@ 123456hotmail.com (A.A.A.); sallam_reem@ 123456yahoo.com (R.M.S.)
                [6 ]Department of Medicine, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia
                [7 ]Clinical Chemistry Unit, Department of Pathology, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia
                Author notes
                [†]

                These authors contributed equally to this work.

                [* ]Authors to whom correspondence should be addressed; E-Mails: aldaghri2011@ 123456gmail.com (N.M.A.-D.); p.g.mcternan@ 123456warwick.ac.uk (P.G.M.); Tel.: +966-1-467-5939 (N.M.A.-D.); +44-2476-96-8587 (P.G.M.); Fax: +966-1-467-5931 (N.M.A.-D.); +44-2476-96-8653 (P.G.M.).
                Article
                nutrients-07-05290
                10.3390/nu7085290
                4555129
                26247966
                0f73c71e-a208-4de6-8f03-c1c48a699ff3
                © 2015 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 25 June 2015
                : 27 July 2015
                Categories
                Article

                Nutrition & Dietetics
                endotoxin,type 2 diabetes mellitus,arab women,high fat meal
                Nutrition & Dietetics
                endotoxin, type 2 diabetes mellitus, arab women, high fat meal

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