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Ethanol and unsaturated fat diet‐induced liver injury is associated with intestinal inflammation in a mouse model of alcoholic liver disease
Author(s) -
Kirpich Irina,
Feng Wenke,
Wang Yuhua,
Liu Yanlong,
Barve Shirish,
McClain Craig
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.825.6
Subject(s) - medicine , alcoholic liver disease , liver injury , intestinal permeability , endocrinology , steatosis , inflammation , triglyceride , fatty liver , liver disease , systemic inflammation , chemistry , cholesterol , disease , cirrhosis
Ethanol‐induced endotoxemia due to disruption of intestinal integrity plays an important role in the alcoholic liver disease (ALD). Linoleic acid (LA), a major unsaturated fatty acid in the American diet, is known to exacerbate alcohol‐induced liver injury. However, the mechanism(s) underlying the deleterious effects of dietary LA in ALD are not fully understood. Materials and Methods C57BL/6N mice were fed either an unsaturated fat (USF, LA enriched) or a saturated fat (SF, medium triglycerides enriched) Lieber‐DeCarli diet (5% EtOH) for 8 weeks. Control mice were pair‐fed on an isocaloric basis. Liver injury and steatosis; systemic and intestinal inflammation as well as intestinal permeability and blood endotoxin levels were evaluated. Results USF+EtOH feeding resulted in significant hepatic triglyceride accumulation and increased plasma ALT levels as a marker of liver injury; increased intestinal permeability (ileal segments) and elevated blood endotoxin levels compared to SF+EtOH and control fed animals. Significantly elevated intestinal TNF‐α and MCP1 mRNA levels as markers of inflammation were also observed only in USF+EtOH group. Conclusion Intestinal inflammation caused by USF+EtOH likely play a critical role in the gut leakiness, elevated blood endotoxemia and consequent liver injury in an animal model of ALD. This work was supported by funding from NIH and VA.