title: Oral administration of immunoglobulin G-enhanced colostrum alleviates insulin resistance and liver injury and is associated with alterations in natural killer T cells.
abstract: Insulin resistance and metabolic syndrome are chronic inflammatory conditions that lead to hepatic injury and non-alcoholic steatohepatitis (NASH). Bovine colostrum has therapeutic effects in a variety of chronic infections. However its effectiveness in NASH was never studied. Natural killer T (NKT) cells have been shown to be associated with some of the pathological and metabolic abnormalities accompanying NASH in leptin-deficient (ob/ob) mice. In the present study, we used hyperimmune bovine colostrum to treat hepatic injury and insulin resistance and we also assessed the effects on NKT cells. We used ob/ob mice that were fed for 6 weeks with either 0·1 mg bovine colostrum prepared from non-immunized cows, 0·1 mg hyperimmune colostrum raised against a bacterial lipopolysaccharide (LPS) extract or 0·001, 0·1 or 1 mg of immunoglobulin (Ig)G purified from hyperimmune colostrum (IgG-LPS). NKT cells were phenotyped by flow cytometry, and hepatic injury and insulin resistance were assessed by measuring fasting glucose levels, glucose tolerance tests and liver enzymes. Fat accumulation was measured in the liver and plasma. Oral administration of hyperimmune colostrums decreased alanine aminotransferase (ALT) serum levels and serum triglycerides compared to controls. Glucose intolerance was also improved by the hyperimmune colostrum preparations. These results were accompanied by a decrease in serum tumour necrosis factor (TNF)-α levels following oral treatment with 0·1 or 1 mg of IgG-LPS. The beneficial effects of hyperimmune colostrums were associated with an increase in the number of splenic NKT cells. These data suggest that oral administration of hyperimmune colostrum preparations can alleviate chronic inflammation, liver injury and insulin resistance associated with NASH.
authors.affiliation: Liver Unit, Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
authors.forename: T
authors.initials: T
authors.lastname: Adar
authors.forename: A
authors.initials: A
authors.lastname: Ben Ya'acov
authors.forename: G
authors.initials: G
authors.lastname: Lalazar
authors.forename: Y
authors.initials: Y
authors.lastname: Lichtenstein
authors.forename: D
authors.initials: D
authors.lastname: Nahman
authors.forename: M
authors.initials: M
authors.lastname: Mizrahi
authors.forename: V
authors.initials: V
authors.lastname: Wong
authors.forename: B
authors.initials: B
authors.lastname: Muller
authors.forename: G
authors.initials: G
authors.lastname: Rawlin
authors.forename: Y
authors.initials: Y
authors.lastname: Ilan
mesh_terms: D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D015415:Biomarkers; D001786:Blood Glucose / Q000032:analysis; D002417:Cattle; D003126:Colostrum / Q000276:immunology*; D004353:Drug Evaluation, Preclinical; D054307:Enterotoxigenic Escherichia coli / Q000276:immunology; D005234:Fatty Liver / Q000097:blood / Q000276:immunology / Q000628:therapy*; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000276:immunology / Q000628:therapy*; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D007167:Immunotherapy; D007249:Inflammation / Q000276:immunology / Q000628:therapy*; D007333:Insulin Resistance / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008820:Mice, Obese; D055611:Natural Killer T-Cells / Q000145:classification / Q000187:drug effects* / Q000276:immunology; D065626:Non-alcoholic Fatty Liver Disease; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D000410:Alanine Transaminase