Postprandial low-grade inflammation does not specifically require TLR4 activation in the rat
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RESEARCH
Open Access
Postprandial low-grade inflammation does not specifically require TLR4 activation in the rat Dominique Hermier* , Véronique Mathé, Annaïg Lan, Clélia Santini, Annie Quignard-Boulangé, Jean-François Huneau and François Mariotti
Abstract Background: Toll-like receptor 4 (TLR4), an innate immune receptor, is suspected to play a key role in the postprandial inflammation that is induced by a high-fat meal rich in saturated fatty acids (SFA). Our objective was to test this hypothesis by using a specific competitive inhibitor of TLR4 (INH) vs vehicle (VEH) administered immediately before a high-SFA meal in rats. Methods: First, in a cross-over kinetic study of 12 rats receiving INH and VEH i.v. 10 min before the test meal, we measured plasma inflammatory and vascular markers for 6 h. Then, in 20 rats, 3 h after INH or VEH followed by the test meal (parallel study), we measured the mRNA level of a set of cytokines (Il1-β, Il-6, Tnfα, Mcp-1, Pai-1), and of Tlr4 and Tlr2 in the adipose tissue and the liver, and that of adhesion molecules (Icam-1 and Vcam-1) in the aorta. Results: Plasma IL-6 and PAI-1 increased >4-fold at 3–4 h after test-meals, very similarly after INH as compared to VEH. The expression of TLR2 and of all measured cytokine genes in the adipose tissue was dramatically higher after INH (vs VEH). In the liver, gene expression of Il1-β, Tnfα, Mcp-1 and Tlr2, was also higher after INH, though more moderately, whereas that of Il-6 and Pai-1 was similar between groups. INH did not affect mRNA level of Icam-1 and Vcam-1 in the aorta. Conclusion: TLR4 activation is not specifically required to mediate systemic postprandial inflammation and we propose that TLR2 and TLR4 exert a dual and interdependent mediation of the postprandial inflammatory response, at least in the adipose tissue. Keywords: Postprandial, Inflammation, TLR, Adipose tissue
Background Epidemiological and experimental data indicate that diets rich in saturated fatty acids (SFA) and simple sugars favour the development of metabolic and physiological dysregulations that characterize the metabolic syndrome and increase the risk of cardiovascular disease and type-2 diabetes [1]. These dysregulations includes oxidative stress, low-grade inflammation and endothelial dysfunction, which are well known as being pivotal to the initiation and progression of the metabolic syndrome. Importantly, in the last decade, a large body of evidence has accumulated demonstrating that a single high-lipid/high-sucrose meal transiently elicits a * Correspondence: [email protected] UMR Physiologie de la Nutrition et du Comportement Alimentaire, AgroParisTech, INRA, Université Paris-Saclay, 16 rue Claude Bernard, F-75005 Paris, France
cluster of low-grade postprandial inflammatory responses (PPIR) [2–5]. PPIR can be measured in plasma as an increased concentration in a number of inflammatory and vascular markers. This plasma increase has been reported in response to a high-fat challenge in healthy human subjects [6, 7] as well as in th
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