title: Deficiency in galectin-3 promotes hepatic injury in CDAA diet-induced nonalcoholic fatty liver disease.
abstract: Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as a condition in which excess fat accumulates in hepatocytes. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD in which inflammation and fibrosis in the liver are noted, may eventually progress to end-stage liver disease. Galectin-3, a β-galactoside-binding animal lectin, is a multifunctional protein. This protein is involved in inflammatory responses and carcinogenesis. We investigated whether galectin-3 is involved in the development of NASH by comparing galectin-3 knockout (gal3(-/-)) mice and wild-type (gal3(+/+)) mice with choline-deficient L-amino-acid-defined (CDAA) diet-induced NAFLD/NASH. Hepatic injury was significantly more severe in the gal3(-/-) male mice, as compared to the gal3(+/+) mice. Data generated by microarray analysis of gene expression suggested that galectin-3 deficiency causes alterations in the expression of various genes associated with carcinogenesis and lipid metabolism. Through canonical pathway analysis, involvement of PDGF and IL-6 signaling pathways was suggested in galectin-3 deficiency. Significant increase of CD14, Fos, and Jun, those that were related to lipopolysaccharide-mediated signaling, was candidate to promote hepatocellular damages in galectin-3 deficiency. In conclusion, galectin-3 deficiency in CDAA diet promotes NAFLD features. It may be caused by alterations in the expression profiles of various hepatic genes including lipopolysaccharide-mediated inflammation.
authors.affiliation: Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. knomoto@med.u-toyama.ac.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nomoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishida
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakanishi
authors.forename: Makoto
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takasaki
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tabuchi
authors.forename: Koichi
authors.initials: K
authors.lastname: Tsuneyama
mesh_terms: D000596:Amino Acids / Q000008:administration & dosage; D000818:Animals; D002794:Choline / Q000008:administration & dosage; D004032:Diet / Q000009:adverse effects*; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D037502:Galectin 3 / Q000172:deficiency / Q000235:genetics*; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D010865:Pilot Projects; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000596:Amino Acids; D037502:Galectin 3; D002794:Choline