Western-diet consumption induces alteration of barrier function mechanisms in the ileum that correlates with metabolic endotoxemia in rats

Abstract

21Obesity and its related disorders have been associated to the presence in the blood of gut bacteria-22 derived lipopolysaccharides (LPS). However, the factors underlying this low-grade elevation in 23 plasma LPS, so-called metabolic endotoxemia, are not fully elucidated. We aimed to investigate the 24 effects of Western diet (WD) feeding on intestinal and hepatic LPS handling mechanisms in a rat 25 model of diet-induced obesity (DIO). Rats were fed either a standard chow diet (C) or a Western Diet 26 (WD, 45% fat) for 6 weeks. They were either fed ad libitum or pair-fed to match the caloric intake of 27 Crats for the first week then fed ad libitum for the remaining 5 weeks. Six-week WD feeding led to a 28 mild obese phenotype with increased adiposity and elevated serum LPS-binding protein (LBP) levels 29 relative to C rats, irrespective of initial energy intake. Serum LPS was not different between dietary 30 groups but exhibited strong variability. Disrupted ileal mucus secretion and decreased ileal Reg3-γ and 31 -β gene expression along with high ileal permeability to LPS were observed in WD compared to C-fed 32 rats. Ileal and caecal intestinal alkaline phosphatase (IAP) activity as well as Verrucomicrobia and 33Bifidobacterium caecal levels were increased in WD-fed rats compared to C-fed rats. WD 34 consumption did not impact mRNA levels of LPS-handling hepatic enzymes. Correlation analysis 35 revealed that ileal passage of LPS, IAP activity, Proteobacteria levels and hepatic aoah gene 36 expression correlated with serum LPS and LBP, suggesting that ileal mucosal defense impairment 37 induced by WD feeding contribute to metabolic endotoxemia. 38 39

Moderate chronic ethanol consumption exerts beneficial effects on nonalcoholic fatty liver in mice fed a high-fat diet: possible role of higher formation of triglycerides enriched in monounsaturated fatty acids

“…This difference was apparently not related to lower food consumption in ethanol-treated obese mice in this period of time ( Figure 1b). HFD induced a transient increase in food consumption (Figure 1b), as already observed in different rodent models of diet-induced obesity (DIO) [33,34]. Caloric intake was lower in SD mice compared with HFD mice and within the latter group, ethanol-treated HFD mice consumed overall more energy than HFD mice (Figure 1c), due to the calories provided by ethanol (7 kcal/g).…”

Chronic nonbacterial prostate inflammation in a rat model is associated with changes of gut microbiota that can be modified with a galactoglucomannan‐rich hemicellulose extract in the diet

“…LPS is difficult to measure from blood samples because it is rapidly bound to blood binding proteins and therefore measuring LPS content often gives unreliable results. Thus, the amount of LBP, which binds free LPS in blood, is an indirect indicator of the LPS load . Our present results show that the amount of LBP in blood was significantly higher in rats with CPI compared to healthy rats, indicating that the amount of LPS in blood is higher.…”

Chronic refined low-fat diet consumption reduces cholecystokinin satiation in rats

“…Similarly, rats implanted with osmotic mini-pumps that chronically deliver LPS for 6 weeks exhibited increased SOCS3 expression in VAN, associated to decreased phosphorylation of signal transducers and activators of transcription 3, another marker of leptin signaling disruption [15]. HF/HS chronic consumption has been shown to induce dysbiosis and alter the intestinal and hepatic mechanisms involved in protection against LPS entry into the organisms, resulting in greater plasma LPS in HF/HS diet fed rats [24]. The impact of LF diet consumption on intestinal barrier function has not been evaluated so far.…”

“…The increased IAP activity observed in LF diet-fed compared to chow-fed rats could be a host adaptive response to altered microbiota composition and increased abundance of LPS-bearing bacteria as observed in DIO rats [24]. LBP is an acute-phase protein synthesized by hepatocytes in response to LPS and released into the bloodstream.…”