title: Western-diet consumption induces alteration of barrier function mechanisms in the ileum that correlates with metabolic endotoxemia in rats.
abstract: Obesity and its related disorders have been associated with the presence in the blood of gut bacteria-derived lipopolysaccharides (LPS). However, the factors underlying this low-grade elevation in plasma LPS, so-called metabolic endotoxemia, are not fully elucidated. We aimed to investigate the effects of Western diet (WD) feeding on intestinal and hepatic LPS handling mechanisms in a rat model of diet-induced obesity (DIO). Rats were fed either a standard chow diet (C) or a Western Diet (WD, 45% fat) for 6 wk. They were either fed ad libitum or pair-fed to match the caloric intake of C rats for the first week, then fed ad libitum for the remaining 5 wk. Six-week WD feeding led to a mild obese phenotype with increased adiposity and elevated serum LPS-binding protein (LBP) levels relative to C rats, irrespective of initial energy intake. Serum LPS was not different between dietary groups but exhibited strong variability. Disrupted ileal mucus secretion and decreased ileal Reg3-γ and -β gene expression along with high ileal permeability to LPS were observed in WD compared with C-fed rats. Ileal and cecal intestinal alkaline phosphatase (IAP) activity as well as Verrucomicrobia and Bifidobacterium cecal levels were increased in WD-fed rats compared with C-fed rats. WD consumption did not impact mRNA levels of LPS-handling hepatic enzymes. Correlation analysis revealed that ileal passage of LPS, IAP activity, Proteobacteria levels and hepaticaoahgene expression correlated with serum LPS and LBP, suggesting that ileal mucosal defense impairment induced by WD feeding contribute to metabolic endotoxemia.
authors.affiliation: Institut Numecan INRA INSERM Université de Rennes 1, Saint-Gilles, France; and.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Guerville
authors.affiliation: Institut Numecan INRA INSERM Université de Rennes 1, Saint-Gilles, France; and.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Leroy
authors.affiliation: Institut Numecan INRA INSERM Université de Rennes 1, Saint-Gilles, France; and.
authors.forename: Annaëlle
authors.initials: A
authors.lastname: Sinquin
authors.affiliation: Univ-Lyon, CarMeN Laboratory, INRA U1397, Université Claude Bernard Lyon 1, Inserm U1060, INSA Lyon, Villeurbanne, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Laugerette
authors.affiliation: Univ-Lyon, CarMeN Laboratory, INRA U1397, Université Claude Bernard Lyon 1, Inserm U1060, INSA Lyon, Villeurbanne, France.
authors.forename: Marie-Caroline
authors.initials: MC
authors.lastname: Michalski
authors.affiliation: Institut Numecan INRA INSERM Université de Rennes 1, Saint-Gilles, France; and gaelle.boudry@inra.fr.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Boudry
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D066273:Diet, Western; D004435:Eating / Q000502:physiology*; D019446:Endotoxemia / Q000378:metabolism* / Q000473:pathology; D005247:Feeding Behavior; D007082:Ileum / Q000378:metabolism* / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009924:Organ Culture Techniques; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar
keywords: intestine; lipopolysaccharides; metabolic endotoxemia; obesity