The type of dietary fat modulates intestinal tight junction integrity, gut permeability, and hepatic Toll-like receptor expression in a mouse model of alcoholic liver disease

Kirpich, Irina A.; Feng, Wenke; Wang, Yuhua; Liu, Yanlong; Barker, David F.; Barve, Shirish S.; McClain, Craig J.

doi:10.1111/j.1530-0277.2011.01673.x

Cited by 135Alcohol Consumption and Health EffectsGastrointestinal motility and disordersGut microbiota and health

The type of dietary fat modulates intestinal tight junction integrity, gut permeability, and hepatic Toll-like receptor expression in a mouse model of alcoholic liver disease

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Kirpich, Irina A., Feng, Wenke, Wang, Yuhua, Liu, Yanlong, Barker, David F., Barve, Shirish S., McClain, Craig J.·2012·Alcoholism Clinical and Experimental Research

DOI 10.1111/j.1530-0277.2011.01673.xPMC PMC3319492

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Abstract

BACKGROUND: Interactions between the gut, immune system, and the liver, as well as the type of fat in the diet, are critical components of alcoholic liver disease (ALD). The goal of the present study was to determine the effects of saturated fat (SF) and unsaturated fat (USF) on ethanol (EtOH)-induced gut-liver interactions in a mouse model of ALD. METHODS: C57BL/6N mice were fed Lieber-DeCarli liquid diets containing EtOH and enriched in USF (corn oil) or SF (medium chain triglycerides:beef tallow). Control mice were pair-fed on an isocaloric basis. Liver injury and steatosis, blood endotoxin levels, intestinal permeability, and tight junction (TJ) integrity, as well as hepatic Toll-like receptor (TLR) gene expression, were evaluated. RESULTS: After 8 weeks of EtOH feeding, liver injury and steatosis were observed in USF + EtOH group compared with control and SF + EtOH. Significantly increased intestinal permeability in conjunction with elevated blood endotoxin levels were observed in the ileal segments of the mice fed USF + EtOH. USF diet alone resulted in down-regulation of intestinal TJ protein mRNA expression compared with SF. Importantly, alcohol further suppressed TJ proteins in USF + EtOH, but did not affect intestinal TJ in SF + EtOH group. The type of fat in the diet alone did not affect hepatic TLR expression. Compared with control animals, hepatic TLR (TLR 1, 2, 3, 4, 7, 8, 9) mRNA expression was significantly (p < 0.05) increased in USF + EtOH, but not in SF + EtOH group. Notably, TLR5 was the only up-regulated TLR in both SF + EtOH and USF + EtOH groups. CONCLUSIONS: Dietary fat is an important cofactor in alcohol-associated liver injury. We demonstrate that USF (corn oil/linoleic acid) by itself results in dysregulation of intestinal TJ integrity leading to increased gut permeability, and alcohol further exacerbates these alterations. We postulate that elevated blood endotoxin levels in response to USF and alcohol in conjunction with up-regulation of hepatic TLRs combine to cause hepatic injury in ALD.

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Binge alcohol exposure promotes gut leakiness.
“binge alcohol exposure [232], [233], [234], [235], [236], [237], [238], [239] and nonalcoholic substances including fructose [240], [241], [242] are known to promote gut leakiness, contributing to more severe inflammatory liver disease.”
From Mitochondrial dysfunction and tissue injury by alcohol, high fat, nonalcoholic substances and pathological conditions through post-translational protein modifications (2014) · cites this paper as [233]

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Hepatic effects of tartrazine (E 102) after systemic exposure are independent of oestrogen receptor interactions in the mouse
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Protective effects of Lactococcus lactis expressing alcohol dehydrogenase and acetaldehyde dehydrogenase on acute alcoholic liver injury in mice
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Docosahexaenoate-enriched fish oil and medium chain triglycerides shape the feline plasma lipidome and synergistically decrease circulating gut microbiome-derived putrefactive postbiotics
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Fat-1 Transgenic Mice With Augmented n3-Polyunsaturated Fatty Acids Are Protected From Liver Injury Caused by Acute-On-Chronic Ethanol Administration
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Macronutrients as Regulators of Intestinal Epithelial Permeability: Where Do We Stand?
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A Corn Oil–Based Diet Protects Against Combined Ethanol and Iron‐Induced Liver Injury in a Mouse Model of Hemochromatosis
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Ileum Gene Expression in Response to Acute Systemic Inflammation in Mice Chronically Fed Ethanol: Beneficial Effects of Elevated Tissue n-3 PUFAs
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Mice lacking α4 nicotinic acetylcholine receptors are protected against alcohol‐associated liver injury
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Ethanol and dietary unsaturated fat (corn oil/linoleic acid enriched) cause intestinal inflammation and impaired intestinal barrier defense in mice chronically fed alcohol
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Dietary fat sources differentially modulate intestinal barrier and hepatic inflammation in alcohol-induced liver injury in rats
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Authors: Kirpich, I. A., Feng, W., Wang, Y., Liu, Y., Barker, D. F., Barve, S. S., & McClain, C. J.
Affiliations: University of Louisville (US)
Corresponding author: McClain, Craig J.
ORCID: Kirpich, Irina A.
Feng, Wenke
Wang, Yuhua
Liu, Yanlong
Barker, David F.
Barve, Shirish S.
McClain, Craig J.
Venue: Alcoholism Clinical and Experimental Research
Publisher: Wiley
Published: 2011-12-07
Volume: 36
Issue: 5
Pages: 835-846
ISSN: 0145-6008 (ISSN-L)
1530-0277
DOI: 10.1111/j.1530-0277.2011.01673.x
PMC: PMC3319492
OpenAlex: W2098539191
Cited by: 135
References: 51
Citations by year: 2025: 11 · 2024: 6 · 2023: 7 · 2022: 12 · 2021: 10 · 2020: 8 · 2019: 8 · 2018: 8 · 2017: 18 · 2016: 11 · 2015: 11 · 2014: 10 · 2013: 11 · 2012: 4
FWCI: 5.61
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Alcoholism Clinical and Experimental Research (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: U.S. Forest Service
U.S. Public Health Service (R01 AAO14371)
National Institute on Alcohol Abuse and Alcoholism (R01AA018016, R37AA010762, U01AA021901, R01AA010496, R21AA020849, P30AA019360, R01AA010762, R01AA015970, R01AA014371, P01AA017103, R01AA018869, R01 AA0015970, RC2AA019385)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK071765)
Topics: Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords: alcoholic liver disease, dietary fat, saturated fat, unsaturated fat, medium-chain triglycerides, corn oil, ethanol, intestinal tight junctions, intestinal permeability, endotoxin, TLR5, liver injury, hepatic steatosis, gut-liver axis
MeSH terms: Ethanol, Animals, Body Composition, Body Weight, Dietary Fats, Unsaturated, Disease Models, Animal, Eating, Endotoxins, Liver, Liver Diseases, Alcoholic, Macrophages, Male, Mice, Inbred C57BL, Permeability, Up-Regulation, Oxidative Stress, Tight Junctions, Gastrointestinal Tract, Toll-Like Receptors, Mice

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The type of dietary fat modulates intestinal tight junction integrity, gut permeability, and hepatic Toll-like receptor expression in a mouse model of alcoholic liver disease

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