Document Detail

Dietary fat sources differentially modulate intestinal barrier and hepatic inflammation in alcohol-induced liver injury in rats.
MedLine Citation:
PMID:  24113767     Owner:  NLM     Status:  MEDLINE    
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.
Wei Zhong; Qiong Li; Guoxiang Xie; Xiuhua Sun; Xiaobing Tan; Xinguo Sun; Wei Jia; Zhanxiang Zhou
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-10-10
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  305     ISSN:  1522-1547     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2013 Dec 
Date Detail:
Created Date:  2013-12-16     Completed Date:  2014-02-13     Revised Date:  2014-07-14    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G919-32     Citation Subset:  IM    
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MeSH Terms
Dietary Fats* / classification,  metabolism
Ethanol / pharmacology*
Feedback, Physiological
Gastrointestinal Tract* / metabolism,  physiopathology
Inflammation / metabolism,  pathology,  prevention & control
Lipid Metabolism
Liver* / metabolism,  pathology
Liver Diseases, Alcoholic* / metabolism,  pathology,  prevention & control
Models, Animal
Rats, Sprague-Dawley
Triglycerides / metabolism
Grant Support
Reg. No./Substance:
0/Dietary Fats; 0/Triglycerides; 3K9958V90M/Ethanol; 8002-31-1/cocoa butter

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