title: Milk osteopontin, a nutritional approach to prevent alcohol-induced liver injury.
abstract: 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.
authors.affiliation: Div. of Liver Diseases, Dept. of Medicine, Mount Sinai School of Medicine, Box 11-23, 1425 Madison Ave., Rm. 11-70, New York, NY 10029, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Ge
authors.forename: Yongke
authors.initials: Y
authors.lastname: Lu
authors.forename: Tung-Ming
authors.initials: TM
authors.lastname: Leung
authors.forename: Esben S
authors.initials: ES
authors.lastname: Sørensen
authors.forename: Natalia
authors.initials: N
authors.lastname: Nieto
mesh_terms: D000818:Animals; D002417:Cattle; D002492:Central Nervous System Depressants / Q000633:toxicity*; D002852:Chromatography, Ion Exchange; D019587:Dietary Supplements; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000473:pathology; D006519:Hepatitis, Alcoholic / Q000473:pathology / Q000517:prevention & control*; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008111:Liver Function Tests; D008112:Liver Glycogen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008894:Milk Proteins / Q000302:isolation & purification / Q000627:therapeutic use*; D009077:Mucins / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D053495:Osteopontin / Q000096:biosynthesis / Q000302:isolation & purification / Q000627:therapeutic use*; D013270:Stomach / Q000473:pathology; D019108:Tight Junctions
chemical_list: D002492:Central Nervous System Depressants; D008112:Liver Glycogen; D008894:Milk Proteins; D009077:Mucins; D053495:Osteopontin; D000431:Ethanol; D052247:Nitric Oxide Synthase Type II
keywords: gut; inflammation; osteopontin; steatosis