Ethanol and dietary unsaturated fat (corn oil/linoleic acid enriched) cause intestinal inflammation and impaired intestinal barrier defense in mice chronically fed alcohol - PubMed (original) (raw)
Ethanol and dietary unsaturated fat (corn oil/linoleic acid enriched) cause intestinal inflammation and impaired intestinal barrier defense in mice chronically fed alcohol
Irina A Kirpich et al. Alcohol. 2013 May.
Abstract
Alcohol and dietary fat both play an important role in alcohol-mediated multi-organ pathology, including gut and liver. In the present study we hypothesized that the combination of alcohol and dietary unsaturated fat (USF) would result in intestinal inflammatory stress and mucus layer alterations, thus contributing to disruption of intestinal barrier integrity. C57BL/6N mice were fed Lieber-DeCarli liquid diets containing EtOH and enriched in USF (corn oil/linoleic acid) or SF (medium chain triglycerides: beef tallow) for 8 weeks. Intestinal histology, morphometry, markers of inflammation, as well as levels of mucus protective factors were evaluated. Alcohol and dietary USF triggered an intestinal pro-inflammatory response, characterized by increase in Tnf-α, MCP1, and MPO activity. Further, alcohol and dietary USF, but not SF, resulted in alterations of the intestinal mucus layer, characterized by decreased expression of Muc2 in the ileum. A strong correlation was observed between down-regulation of the antimicrobial factor Cramp and increased Tnf-α mRNA. Therefore, dietary unsaturated fat (corn oil/LA enriched) is a significant contributing factor to EtOH-mediated intestinal inflammatory response and mucus layer alterations in rodents.
Copyright © 2013 Elsevier Inc. All rights reserved.
Figures
Figure 1. Evaluation of the intestinal pathology in response to ethanol and saturated fat (SF) or unsaturated fat (USF) diets
(A-B) Representative microphotographs of hematoxylin and eosin staining of the intestinal sections. Distal ileum from mice fed Lieber-DeCarli control and EtOH liquid diets for 8 weeks. Sections were analyzed using a light microscope (original magnification for A: x200, for B:x400). The mucosa appear normal in SF and USF groups (A-1, and A-3). Histological injury is noted in mice fed alcohol, characterized by shorten villi (A-2, and A-4). Inflammatory cell infiltrates (B-1) and dilation of blood vessels (B-2) were observed predominantly in the lamina propria of USF+EtOH group. Arrows indicate infiltration of lymphocytes and neutrophils, and dilated capillaries. (C-D) Morphometrical analysis of the ileal mucosa in response to ethanol and dietary fat. Ten complete villus-crypt junctions of the ileal segments of the individual mouse were measured, n=3 animals/per group. Values are mean+SEM. The value for the SF group was set at 1 as a control for comparison purposes. Statistical differences were analyzed by two-way ANOVA followed by the Tukey’s multiple comparison test. Means without a common letter differ at p<0.05.
Figure 2. Intestinal markers of inflammation in response to alcohol and saturated fat (SF) and unsaturated fat (USF) diets
(A and B) Tnf-α mRNA and protein levels. (C and D) Mcp1 mRNA and protein levels. The relative mRNA expression was measured by qRT-PCR. Values are mean+SEM, n=6 animals/per group. Cytokine protein levels were determined using MILLIPLEX Cytokine/Chemokine Panel kit (Millipore, Billerica, MA) on the Luminex100 IS System (Austin, TX). Values are mean+SEM, n=6–9 animals/per group. Statistical differences were analyzed by two-way ANOVA followed by the Tukey’s multiple comparison test. Means without a common letter differ at p<0.05.
Figure 3. Intestinal MPO activity in response to EtOH and SF and USF dietary fat
USF+EtOH significantly increased ileal MPO activity, a marker of inflammation and neutrophil infiltration, compared with SF+EtOH. Values are mean+SEM, n=5–6 animals/per group. Statistical differences were analyzed by two-way ANOVA followed by the Tukey’s multiple comparison test. Means without a common letter differ at p<0.05.
Figure 4. Effects of saturated fat (SF) or unsaturated fat (USF) on the intestinal mucus layer integrity in response to chronic alcohol feeding
(A) Quantitative analysis of intestinal Goblet cells. (B) Muc2 mRNA levels assessed by qRT-PCR. Values are mean+SEM, n=6 animals/per group. Statistical differences were analyzed by two-way ANOVA followed by the Tukey’s multiple comparison test. Means without a common letter differ at p<0.05.
Figure 5. Down-regulation of the intestinal mucosa antimicrobial peptide, Cramp, in response to ethanol and dietary unsaturated but not saturated fat
(A) Cramp mRNA levels assessed by qRT-PCR. Values are mean+SEM, n=6 animals/per group. Statistical differences were analyzed by two-way ANOVA followed by the Tukey’s multiple comparison test. Means without a common letter differ at p<0.05. (B) Negative correlation was observed between intestinal antimicrobial factor Cramp and intestinal Tnf-α mRNA levels.
Similar articles
- 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 IA, Feng W, Wang Y, Liu Y, Barker DF, Barve SS, McClain CJ. Kirpich IA, et al. Alcohol Clin Exp Res. 2012 May;36(5):835-46. doi: 10.1111/j.1530-0277.2011.01673.x. Epub 2011 Dec 7. Alcohol Clin Exp Res. 2012. PMID: 22150547 Free PMC article. - Effects of type of dietary fat on phorbol ester-elicited tumor promotion and other events in mouse skin.
Leyton J, Lee ML, Locniskar M, Belury MA, Slaga TJ, Bechtel D, Fischer SM. Leyton J, et al. Cancer Res. 1991 Feb 1;51(3):907-15. Cancer Res. 1991. PMID: 1899048 - Dietary Linoleic Acid and Its Oxidized Metabolites Exacerbate Liver Injury Caused by Ethanol via Induction of Hepatic Proinflammatory Response in Mice.
Warner DR, Liu H, Miller ME, Ramsden CE, Gao B, Feldstein AE, Schuster S, McClain CJ, Kirpich IA. Warner DR, et al. Am J Pathol. 2017 Oct;187(10):2232-2245. doi: 10.1016/j.ajpath.2017.06.008. Am J Pathol. 2017. PMID: 28923202 Free PMC article. - Preservation of hepatocyte nuclear factor-4α contributes to the beneficial effect of dietary medium chain triglyceride on alcohol-induced hepatic lipid dyshomeostasis in rats.
Li Q, Zhong W, Qiu Y, Kang X, Sun X, Tan X, Zhao Y, Sun X, Jia W, Zhou Z. Li Q, et al. Alcohol Clin Exp Res. 2013 Apr;37(4):587-98. doi: 10.1111/acer.12013. Epub 2012 Nov 5. Alcohol Clin Exp Res. 2013. PMID: 23126616 Free PMC article.
Cited by
- The effects of some natural products compared to synthetic products on the metabolic activity, proliferation, viability, migration, and wound healing in sheep tenocytes.
Al-Shudiefat AAS, Am Alzyoud J, Al Najjar SA, Talat S, Bustanji Y, Abu-Irmaileh B. Al-Shudiefat AAS, et al. Saudi J Biol Sci. 2022 Sep;29(9):103391. doi: 10.1016/j.sjbs.2022.103391. Epub 2022 Jul 22. Saudi J Biol Sci. 2022. PMID: 35942163 Free PMC article. - Gut microbiota-modulating agents in alcoholic liver disease: Links between host metabolism and gut microbiota.
Jung JH, Kim SE, Suk KT, Kim DJ. Jung JH, et al. Front Med (Lausanne). 2022 Jul 22;9:913842. doi: 10.3389/fmed.2022.913842. eCollection 2022. Front Med (Lausanne). 2022. PMID: 35935787 Free PMC article. Review. - Skeletal muscle satellite cell-derived mesenchymal stem cells ameliorate acute alcohol-induced liver injury.
Chung JS, Hwang S, Hong JE, Jo M, Rhee KJ, Kim S, Jung PY, Yoon Y, Kang SH, Ryu H, Kim MY, Bae KS, Eom YW. Chung JS, et al. Int J Med Sci. 2022 Jan 24;19(2):353-363. doi: 10.7150/ijms.68971. eCollection 2022. Int J Med Sci. 2022. PMID: 35165521 Free PMC article. - Human Beta Defensin 2 Ameliorated Alcohol-Associated Liver Disease in Mice.
Warner JB, Larsen IS, Hardesty JE, Song YL, Warner DR, McClain CJ, Sun R, Deng Z, Jensen BAH, Kirpich IA. Warner JB, et al. Front Physiol. 2022 Jan 27;12:812882. doi: 10.3389/fphys.2021.812882. eCollection 2021. Front Physiol. 2022. PMID: 35153819 Free PMC article. - Ileum Gene Expression in Response to Acute Systemic Inflammation in Mice Chronically Fed Ethanol: Beneficial Effects of Elevated Tissue n-3 PUFAs.
Hardesty JE, Warner JB, Song YL, Rouchka EC, McClain CJ, Warner DR, Kirpich IA. Hardesty JE, et al. Int J Mol Sci. 2021 Feb 4;22(4):1582. doi: 10.3390/ijms22041582. Int J Mol Sci. 2021. PMID: 33557303 Free PMC article.
References
- Alzoghaibi MA, Walsh SW, Willey A, Yager DR, Fowler AA, 3rd, Graham MF. Linoleic acid induces interleukin-8 production by Crohn's human intestinal smooth muscle cells via arachidonic acid metabolites. Am. J. Physiol. Gastroint. Liver Physiol. 2004;286:G528–G537. - PubMed
- Amin PB, Diebel LN, Liberati DM. Dose-dependent effect of ethanol and E.Coli on gut permeability and cytokine production. J. Surg. Res. 2009;157:187–192. - PubMed
- Banan A, Choudhary S, Zhang Y, Fields JZ, Keshavarzian A. Ethanol-induced barrier dysfunction and its prevention by growth factors in human intestinal monolayers: evidence for oxidative and cytoskeletal mechanisms. JPharmacol. Exp. Ther. 1999;291:1075–1085. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
- U01 AA021901/AA/NIAAA NIH HHS/United States
- R21 AA020849-01A1/AA/NIAAA NIH HHS/United States
- P01 AA017103/AA/NIAAA NIH HHS/United States
- R01 AA018869/AA/NIAAA NIH HHS/United States
- RC2AA019385/AA/NIAAA NIH HHS/United States
- P30 AA019360/AA/NIAAA NIH HHS/United States
- R01 AA015970/AA/NIAAA NIH HHS/United States
- R01 AA0015970/AA/NIAAA NIH HHS/United States
- R01 AA021978/AA/NIAAA NIH HHS/United States
- R37 AA010762/AA/NIAAA NIH HHS/United States
- R01 AA018016/AA/NIAAA NIH HHS/United States
- R21 AA020849/AA/NIAAA NIH HHS/United States
- R01 DK071765/DK/NIDDK NIH HHS/United States
- RC2 AA019385/AA/NIAAA NIH HHS/United States
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous