Milk osteopontin, a nutritional approach to prevent alcohol-induced liver injury

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  • Xiaodong Ge, Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, United States
  • Yongke Lu, Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, United States
  • Tung-Ming Leung, Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, United States
  • Esben Skipper Sørensen
  • Natalia Nieto, Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, United States
Alcohol consumption is a leading cause of liver disease worldwide; thus, there is an urgent need to develop novel therapeutic interventions. Key events for the onset and progression of alcoholic liver disease result in part from the gut-to-liver interaction. Osteopontin is a cytokine present at high concentration in human milk, umbilical cord, and infants' plasma with beneficial potential. We hypothesized that dietary administration of milk osteopontin could prevent alcohol-induced liver injury perhaps by maintaining gut integrity and averting hepatic inflammation and steatosis. Wild-type mice were fed either the control or the ethanol Lieber-DeCarli diets alone or in combination with milk osteopontin for 3 wk, and parameters of gut and liver damage were measured. Milk osteopontin protected the stomach and the gut by increasing gland height, crypt cell plus enterocyte proliferation, and mucin content in addition to lowering macrophages, plasmacytes, lymphocytes, and neutrophils in the mucosa and submucosa in alcohol-fed mice. Milk osteopontin targeted the gut-liver axis, preserving the expression of tight-junction proteins in alcohol-fed mice thus maintaining intestinal integrity and permeability. There was protection from liver injury since transaminases, the activity scores, triglyceride levels, neutrophil infiltration, 3-nitrotyrosine residues, lipid peroxidation end products, translocation of gram-negative bacteria, lipopolysaccharide levels, and tumor necrosis factor-α were lower in cotreated than in ethanol-fed mice. Furthermore, milk osteopontin diminished ethanol-mediated liver injury in OPN knockout mice. Milk osteopontin could be a simple effective nutritional therapeutic strategy to prevent alcohol hepatotoxicity due, among others, to gut protective, anti-inflammatory, and anti-steatotic actions.
Original languageEnglish
JournalAmerican Journal of Physiology: Gastrointestinal and Liver Physiology
Volume304
Issue10
Pages (from-to)G929-G939
Number of pages10
ISSN0193-1857
DOIs
Publication statusPublished - 15 May 2013

    Research areas

  • Animals, Cattle, Central Nervous System Depressants, Chromatography, Ion Exchange, Dietary Supplements, Ethanol, Female, Gastrointestinal Tract, Hepatitis, Alcoholic, Immunohistochemistry, Liver, Liver Function Tests, Liver Glycogen, Mice, Mice, Inbred C57BL, Milk Proteins, Mucins, Neutrophil Infiltration, Nitric Oxide Synthase Type II, Osteopontin, Stomach, Tight Junctions

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