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Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: Role of endotoxin

Published:March 14, 2008DOI:https://doi.org/10.1016/j.jhep.2008.01.035

      Background/Aims

      Consumption of refined carbohydrates in soft drinks has been postulated to be a key factor in the development of non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to test the effects of ad libitum access to different sugars consumed in drinking water on hepatic fat accumulation.

      Methods

      For 8 weeks, C57BL/J6 mice had free access to solutions containing 30% glucose, fructose, sucrose, or water sweetened with artificial sweetener (AS) or plain water. Body weight, caloric intake, hepatic steatosis and lipid peroxidation were assessed.

      Results

      Total caloric intake and weight gain were highest in mice exposed to glucose. In contrast, hepatic lipid accumulation was significantly higher in mice consuming fructose compared to all other groups. Moreover, endotoxin levels in portal blood and lipid peroxidation as well as TNFα expression were significantly higher in fructose fed mice than in all other groups. Concomitant treatment of fructose fed mice with antibiotics (e.g., polymyxin B and neomycin) markedly reduced hepatic lipid accumulation in fructose fed mice.

      Conclusions

      These data support the hypothesis that high fructose consumption may not only lead to liver damage through overfeeding but also may be directly pro-inflammatory by increasing intestinal translocation of endotoxin.

      Abbreviations:

      TNFα (tumor necrosis factor alpha), IκBα (inhibitor of kappa B alpha), NFκB (nuclear factor kappa B), ROS (reactive oxygen species), SREBP1 (sterol regulator binding protein 1), FAS (fatty acid synthase), PEPCK (phosphoenolpyruvate carboxykinase)

      Keywords

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      References

        • Bedogni G.
        • Miglioli L.
        • Masutti F.
        • Tiribelli C.
        • Marchesini G.
        • Bellentani S.
        Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study.
        Hepatology. 2005; 42: 44-52
        • Adams L.A.
        • Lymp J.F.
        • St Sauver J.
        • Sanderson S.O.
        • Lindor K.D.
        • Feldstein A.
        • et al.
        The natural history of nonalcoholic fatty liver disease: a population-based cohort study.
        Gastroenterology. 2005; 129: 113-121
        • Gross L.S.
        • Li L.
        • Ford E.S.
        • Liu S.
        Increased consumption of refined carbohydrates and the epidemic of type 2 diabetes in the United States: an ecologic assessment.
        Am J Clin Nutr. 2004; 79: 774-779
        • Schulze M.B.
        • Manson J.E.
        • Ludwig D.S.
        • Colditz G.A.
        • Stampfer M.J.
        • Willett W.C.
        • et al.
        Sugar-sweetened beverages, weight gain, and incidence of type 2 diabetes in young and middle-aged women.
        JAMA. 2004; 292: 927-934
        • Ackerman Z.
        • Oron-Herman M.
        • Grozovski M.
        • Rosenthal T.
        • Pappo O.
        • Link G.
        • et al.
        Fructose-induced fatty liver disease: hepatic effects of blood pressure and plasma triglyceride reduction.
        Hypertension. 2005; 45: 1012-1018
        • Jurgens H.
        • Haass W.
        • Castaneda T.R.
        • Schurmann A.
        • Koebnick C.
        • Dombrowski F.
        • et al.
        Consuming fructose-sweetened beverages increases body adiposity in mice.
        Obes Res. 2005; 13: 1146-1156
        • Faeh D.
        • Minehira K.
        • Schwarz J.M.
        • Periasami R.
        • Seongsu P.
        • Tappy L.
        Effect of fructose overfeeding and fish oil administration on hepatic de novo lipogenesis and insulin sensitivity in healthy men.
        Diabetes. 2005; 54: 1907-1913
        • Lewis G.F.
        • Murdoch S.
        • Uffelman K.
        • Naples M.
        • Szeto L.
        • Albers A.
        • et al.
        Hepatic lipase mRNA, protein, and plasma enzyme activity is increased in the insulin-resistant, fructose-fed Syrian golden hamster and is partially normalized by the insulin sensitizer rosiglitazone.
        Diabetes. 2004; 53: 2893-2900
        • Aoyama Y.
        • Yoshida A.
        • Ashida K.
        Effect of dietary fats and fatty acids on the liver lipid accumulation induced by feeding a protein-repletion diet containing fructose to protein-depleted rats.
        J Nutr. 1974; 104: 741-746
        • Diehl A.M.
        • Goodman Z.
        • Ishak K.G.
        Alcohol like liver disease in nonalcoholics. A clinical and histologic comparison with alcohol-induced liver injury.
        Gastroenterology. 1988; 95: 1056-1062
        • Wigg A.J.
        • Roberts-Thomson I.C.
        • Dymock R.B.
        • McCarthy P.J.
        • Grose R.H.
        • Cummins A.G.
        The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor alpha in the pathogenesis of non-alcoholic steatohepatitis.
        Gut. 2001; 48: 206-211
        • Soza A.
        • Riquelme A.
        • Gonzalez R.
        • Alvarez M.
        • Perez-Ayuso R.M.
        • Glasinovic J.C.
        • et al.
        Increased orocecal transit time in patients with nonalcoholic fatty liver disease.
        Dig Dis Sci. 2005; 50: 1136-1140
        • Li Z.
        • Yang S.
        • Lin H.
        • Huang J.
        • Watkins P.A.
        • Moser A.B.
        • et al.
        Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease.
        Hepatology. 2003; 37: 343-350
        • Cope K.
        • Risby T.
        • Diehl A.M.
        Increased gastrointestinal ethanol production in obese mice: implications for fatty liver disease pathogenesis.
        Gastroenterology. 2000; 119: 1340-1347
        • Brun P.
        • Castagliuolo I.
        • Di Leo V.
        • Buda A.
        • Pinzani M.
        • Palu’ G.
        • et al.
        Increased intestinal permeability in obese mice: new evidences in the pathogenesis of nonalcoholic steatohepatitis.
        Am J Physiol Gastrointest Liver Physiol. 2007; 292: G518-G525
        • Emmelot C.H.
        • van der W.D.
        The dose at which neomycin and polymyxin B can be applied for selective decontamination of the digestive tract in mice.
        J Hyg (Lond). 1980; 84: 331-340
        • Wiegersma N.
        • Jansen G.
        • van der W.D.
        Effect of twelve antimicrobial drugs on the colonization resistance of the digestive tract of mice and on endogenous potentially pathogenic bacteria.
        J Hyg (Lond). 1982; 88: 221-230
        • Bergheim I.
        • Guo L.
        • Davis M.A.
        • Lambert J.C.
        • Beier J.I.
        • Duveau I.
        • et al.
        Metformin prevents alcohol-induced liver injury in the mouse: critical role of plasminogen activator inhibitor-1.
        Gastroenterology. 2006; 130: 2099-2112
        • McKim S.E.
        • Konno A.
        • Gabele E.
        • Uesugi T.
        • Froh M.
        • Sies H.
        • et al.
        Cocoa extract protects against early alcohol-induced liver injury in the rat.
        Arch Biochem Biophys. 2002; 406: 40-46
        • Armutcu F.
        • Coskun O.
        • Gurel A.
        • Kanter M.
        • Can M.
        • Ucar F.
        • et al.
        Thymosin alpha 1 attenuates lipid peroxidation and improves fructose-induced steatohepatitis in rats.
        Clin Biochem. 2005; 38: 540-547
        • Arteel G.E.
        Oxidants and antioxidants in alcohol-induced liver disease.
        Gastroenterology. 2003; 124: 778-790
        • Elliott S.S.
        • Keim N.L.
        • Stern J.S.
        • Teff K.
        • Havel P.J.
        Fructose, weight gain, and the insulin resistance syndrome.
        Am J Clin Nutr. 2002; 76: 911-922
        • Bray G.A.
        • Nielsen S.J.
        • Popkin B.M.
        Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity.
        Am J Clin Nutr. 2004; 79: 537-543
        • Hollingsworth K.G.
        • Abubacker M.Z.
        • Joubert I.
        • Allison M.E.
        • Lomas D.J.
        Low-carbohydrate diet induced reduction of hepatic lipid content observed with a rapid non-invasive MRI technique.
        Br J Radiol. 2006; 79: 712-715
        • Deng Q.G.
        • She H.
        • Cheng J.H.
        • French S.W.
        • Koop D.R.
        • Xiong S.
        • et al.
        Steatohepatitis induced by intragastric overfeeding in mice.
        Hepatology. 2005; 42: 905-914
        • Levi B.
        • Werman M.J.
        Long-term fructose consumption accelerates glycation and several age-related variables in male rats.
        J Nutr. 1998; 128: 1442-1449
        • Lin H.Z.
        • Yang S.Q.
        • Chuckaree C.
        • Kuhajda F.
        • Ronnet G.
        • Diehl A.M.
        Metformin reverses fatty liver disease in obese, leptin-deficient mice.
        Nat Med. 2000; 6: 998-1003
        • Kugelmas M.
        • Hill D.B.
        • Vivian B.
        • Marsano L.
        • McClain C.J.
        Cytokines and NASH: a pilot study of the effects of lifestyle modification and vitamin E.
        Hepatology. 2003; 38: 413-419
        • Eastin C.E.
        • McClain C.J.
        • Lee E.Y.
        • Bagby G.J.
        • Chawla R.K.
        Choline deficiency augments and antibody to tumor necrosis factor-alpha attenuates endotoxin-induced hepatic injury.
        Alcohol Clin Exp Res. 1997; 21: 1037-1041
        • Dela Peña A.
        • Leclercq I.
        • Field J.
        • George J.
        • Jones B.
        • Farrell G.
        NF-kappaB activation, rather than TNF, mediates hepatic inflammation in a murine dietary model of steatohepatitis.
        Gastroenterology. 2005; 129: 1663-1674
        • Nosova T.
        • Jokelainen K.
        • Kaihovaara P.
        • Jousimies-Somer H.
        • Siitonen A.
        • Heine R.
        • et al.
        Aldehyde dehydrogenase activity and acetate production by aerobic bacteria representing the normal flora of human large intestine.
        Alcohol Alcohol. 1996; 31: 555-564
        • Nair S.
        • Cope K.
        • Risby T.H.
        • Diehl A.M.
        Obesity and female gender increase breath ethanol concentration: potential implications for the pathogenesis of nonalcoholic steatohepatitis.
        Am J Gastroenterol. 2001; 96: 1200-1204