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

In human nutrition, optimized the status of n-3 long-chain polyunsaturated fatty acids (LCPUFA) and especially docosahexaenoic acid (DHA) during growth appears to be one of the most important goal. We investigated the potential impact of a partial incorporation of dairy lipids (DL) in the diet to increase the n-3 LCPUFA content in tissues, compared to a mixture of vegetable oils. Rats were fed with vegetable oil diet or DL diet, supplemented or not supplemented with DHA, from weaning for 6 weeks. All diets provided the same quantity of 2.3% of total fatty acids of precursor α-linolenic acid. LCPUFA levels in brain, retina, liver, heart, red blood cells and epididymal adipose tissue, Δ-6 desaturase activity and mRNA expression in liver, and plasma cholesterol were measured. Rats fed a DL diet increased their DHA content in brain and retina compared with rats fed a vegetable oil diet and reached the same level than rats directly supplemented with DHA. The status of n-3 docosapentaenoic acid increased with DL diet in heart, red blood cells and liver. The n-3 docosapentaenoic acid specifically discriminated DL diets in the heart. DL diet increased α-linolenic acid content in liver and epididymal adipose tissue, provided specific fatty acids as short- and medium-chain fatty acids and myristic acid, and increased plasma cholesterol. We hypothesized that dairy lipids may increase the n-3 LCPUFA enrichment in tissues by preserving precursor α-linolenic acid from β-mitochondrial oxidation, associated with the presence of short- and medium-chain fatty acids in DL diets. In conclusion, a partial incorporation of dairy lipids in the diet with an adequate α-linolenic acid content improved the n-3 LCPUFA status, especially DHA in brain and retina.