Oral administration of immunoglobulin G-enhanced colostrum alleviates insulin resistance and liver injury and is associated with alterations in natural killer T cells

Abstract

SummaryInsulin 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)-a 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.

A role for whey-derived lactoferrin and immunoglobulins in the attenuation of obesity-related inflammation and disease

“…Significant decreases total cholesterol (6.33 ± 0.1 mmol/L v 5.97 ± 0.7 mmol/L) and LDL cholesterol (4.12 ± 0.6 mmol/L v 3.84 ± 0.6 mmol/L) were noted post-supplementation for the treatment group (Earnest et al, 2005). The exact mechanisms by which bIgs mediate these effects is not known, however multiple mediators are suspected, including the direct binding of bIgs to cholesterol in the intestinal lumen and binding of bIgs to LPS preventing endotoxin-mediated lipogenesis (Earnest et al, 2005) and inflammation (Adar et al, 2012). These studies provide evidence that the use of immunoglobulins may have therapeutic efficacy in obesity-related metabolic dysfunction.…”

“…An animal model utilizing leptin deficient ob/ob mice have documented the effects of eight weeks of supplementation with IgGrich colostrum from cows immunized against enterotoxigenic E.Coli or the purified anti-LPS IgG alone on blood lipids, glucose tolerance and hepatic steatosis (Adar et al, 2012). Reductions in circulating triglycerides (but not total cholesterol) and hepatic fat were noted following supplementation with either the IgG-rich colostrum or the purified IgG, in addition to improved glucose tolerance following supplementation with the purified IgG, all suggesting the potential for bovine immunoglobulin supplementation to affect indices of metabolic disease.…”

Compounds of the sphingomyelin-ceramide-glycosphingolipid pathways as secondary messenger molecules: new targets for novel therapies for fatty liver disease and insulin resistance

“…Oral administration of anti-LPS antibodies along with GSLenriched adjuvant compounds was effective in ameliorating NASH and diabetes in both animal models and humans (2,3,120,124,193,194). These effects were associated with alterations of Tregs and NKT cells, thereby supporting a potential effect of GSLs on the gut-microbiome-immune system axis.…”

“…These patients have altered humoral and cellular immune profiles, including altered NKT cell numbers and function. Data from GD suggest an effect of GC on the cell membrane; hence, some patients have increased red blood cell aggregation due to changes in the properties of the cell membrane (1,2,89). Studies of these patients has implied that GC is involved in NKT cell regulation (90,105,109).…”

“…These molecules have effect in signal transduction and in the pathogenesis of several diseases (1,2,76,80,92,96). Cer is the simplest molecule in this family, and it serves as a precursor for the synthesis of the three main types of complex SLs (SMs, GSLs, and gangliosides), respectively.…”