title: Lactoferrin dampens high-fructose corn syrup-induced hepatic manifestations of the metabolic syndrome in a murine model.
abstract: Hepatic manifestations of the metabolic syndrome are related obesity, type 2 diabetes/insulin resistance and non-alcoholic fatty liver disease. Here we investigated how the anti-inflammatory properties of lactoferrin can protect against the onset of hepatic manifestations of the metabolic syndrome by using a murine model administered with high-fructose corn syrup. Our results show that a high-fructose diet stimulates intestinal bacterial overgrowth and increases intestinal permeability, leading to the introduction of endotoxin into blood circulation and liver. Immunohistochemical staining of Toll-like receptor-4 and thymic stromal lymphopoietin indicated that lactoferrin can modulate lipopolysaccharide-mediated inflammatory cascade. The important regulatory roles are played by adipokines including interleukin-1β, interleukin-6, tumor necrosis factor-α, monocyte chemotactic protein-1, and adiponectin, ultimately reducing hepatitis and decreasing serum alanine aminotransferase release. These beneficial effects of lactoferrin related to the downregulation of the lipopolysaccharide-induced inflammatory cascade in the liver. Furthermore, lactoferrin reduced serum and hepatic triglycerides to prevent lipid accumulation in the liver, and reduced lipid peroxidation, resulting in 4-hydroxynonenal accumulation. Lactoferrin reduced oral glucose tolerance test and homeostasis model assessment-insulin resistance. Lactoferrin administration thus significantly lowered liver weight, resulting from a decrease in the triglyceride and cholesterol synthesis that activates hepatic steatosis. Taken together, these results suggest that lactoferrin protected against high-fructose corn syrup induced hepatic manifestations of the metabolic syndrome.
authors.affiliation: Department of Animal Science and Biotechnology, Tunghai University, Taichung, Taiwan.
authors.forename: Yi-Chieh
authors.initials: YC
authors.lastname: Li
authors.affiliation: Department of Animal Science and Biotechnology, Tunghai University, Taichung, Taiwan.
authors.forename: Chang-Chi
authors.initials: CC
authors.lastname: Hsieh
mesh_terms: D054392:Adipokines / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005951:Glucose Tolerance Test; D066248:High Fructose Corn Syrup / Q000009:adverse effects*; D007150:Immunohistochemistry; D007333:Insulin Resistance / Q000502:physiology; D007781:Lactoferrin / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D054392:Adipokines; D016207:Cytokines; D066248:High Fructose Corn Syrup; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014280:Triglycerides; D000410:Alanine Transaminase; D007781:Lactoferrin; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse