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Dietary fat sources differentially modulate intestinal barrier and hepatic inflammation in alcohol-induced liver injury in rats.

ABSTRACT: Endotoxemia is a causal factor in the development of alcoholic liver injury. The present study aimed at determining the interactions of ethanol with different fat sources at the gut-liver axis. Male Sprague-Dawley rats were pair fed control or ethanol liquid diet for 8 wk. The liquid diets were based on a modified Lieber-DeCarli formula, with 30% total calories derived from corn oil (rich in polyunsaturated fatty acids). To test the effects of saturated fats, corn oil in the ethanol diet was replaced by either cocoa butter (CB, rich in long-chain saturated fatty acids) or medium-chain triglycerides (MCT, exclusively medium-chain saturated fatty acids). Ethanol feeding increased hepatic lipid accumulation and inflammatory cell infiltration and perturbed hepatic and serum metabolite profiles. Ethanol feeding with CB or MCT alleviated ethanol-induced liver injury and attenuated ethanol-induced metabolic perturbation. Both CB and MCT also normalized ethanol-induced hepatic macrophage activation, cytokine expression, and neutrophil infiltration. Ethanol feeding elevated serum endotoxin level, which was normalized by MCT but not CB. In accordance, ethanol-induced downregulations of intestinal occludin and zonula occludens-1 were normalized by MCT but not CB. However, CB normalized ethanol-increased hepatic endotoxin level in association with upregulation of an endotoxin detoxifying enzyme, argininosuccinate synthase 1 (ASS1). Knockdown ASS1 in H4IIEC3 cells resulted in impaired endotoxin clearance and upregulated cytokine expression. These data demonstrate that the protection of saturated fats against alcohol-induced liver injury occur via different actions at the gut-liver axis and are chain length dependent.

SUBMITTER: Zhong W

PROVIDER: S-EPMC3882440 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Dietary fat sources differentially modulate intestinal barrier and hepatic inflammation in alcohol-induced liver injury in rats.

Zhong Wei W Li Qiong Q Xie Guoxiang G Sun Xiuhua X Tan Xiaobing X Sun Xinguo X Jia Wei W Zhou Zhanxiang Z

American journal of physiology. Gastrointestinal and liver physiology 20131010 12

Endotoxemia is a causal factor in the development of alcoholic liver injury. The present study aimed at determining the interactions of ethanol with different fat sources at the gut-liver axis. Male Sprague-Dawley rats were pair fed control or ethanol liquid diet for 8 wk. The liquid diets were based on a modified Lieber-DeCarli formula, with 30% total calories derived from corn oil (rich in polyunsaturated fatty acids). To test the effects of saturated fats, corn oil in the ethanol diet was rep ...[more]

PMID: 24113767

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Project description:Given the key role of methionine in biological processes, adequate methionine should be provided to meet the nutritional requirements. DL-2-hydroxy-4-(methylthio)-butanoic acid (DL-HMTBA) has been considered as an important source of methionine. However, the effects of different sources and levels of methionine on the intestinal health status have not been clarified yet. An experiment was carried out to investigate the effects of different dietary sources and levels of methionine on the intestinal epithelial barrier, inflammatory cytokines expression, ileal morphology, microbiota composition, and cecal short chain fatty acids (SCFA) profiles. For this purpose, 720 male Arbor Acre broiler chicks at 1 d old were randomly assigned to a 2 × 3 factorial arrangement with 2 methionine sources (DL-methionine and DL-HMTBA) and 3 total sulfur amino acids (TSAA) levels (80%, 100%, and 120% of Arbor Acre recommendation). The results showed that DL-HMTBA supplementation promoted intestinal physical barrier at both gene expression level of claudin-1 and serum diamine oxidase level (P < 0.05), and the inflammatory cytokine IL-6 mRNA expression was down-regulated by dietary DL-HMTBA supplementation compared with the DL-methionine group (P < 0.05). Meanwhile, an upregulated gene expression of claudin-1 and zonula occluden-1 (ZO-1) were observed in the low-TSAA treatment on d 14 (P < 0.05), whereas this treatment increased the expression of IL-1β and IL-6 (P < 0.05). Villus height to crypt depth ratio was high (P < 0.05) in the middle-level TSAA group. Furthermore, DL-HMTBA supplementation optimized the microbiota of the ileum especially the relative abundance of Lactobacillus, where the digestion and absorption were completed, and elevated the concentrations of SCFA (acetate, propionate, and butyrate) in the cecal content on d 21 (P < 0.01). In conclusion, dietary DL-HMTBA supplementation improved the intestinal barrier function, immune homeostasis and optimized the microbiota to promote intestinal health status in broiler chickens.

Dataset Information

Dietary fat sources differentially modulate intestinal barrier and hepatic inflammation in alcohol-induced liver injury in rats.

Publications

Dietary fat sources differentially modulate intestinal barrier and hepatic inflammation in alcohol-induced liver injury in rats.

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