Role of immunodeficient animal models in the development of fructose induced NAFLD.
Cellular and humoral immunity had been implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). This study was designed to assess if T, B and natural killer (NK) cells are involved in the progress of NAFLD in mouse models after chronic fructose treatment. Mouse models that are deficient in either T cells, B cells or NK cells or lacking both T and B cells were fed with 30% fructose solution for 12 weeks. Typical features of NAFLD, including the relative body weight, food and water intake, biochemical analytes, liver histology, NAFLD activity score, and glucose tolerance and insulin tolerance test were characterized. Further, the percentage of CD3, B220 and NK cells in peripheral-blood mononuclear cell, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, immunodetection for hepatic apoptosis (p53) and for inflammation (TNFα) and quantitative real-time polymerase chain reaction for putative and inflammatory genes involved were determined. Our results conclude that mice deficient in T cells or NK cells fail to develop fructose induced NAFLD whereas the immunocompetent mice and mice with B-cell-specific defect developed NAFLD. Taken together, these data support that the onset of fructose-induced NAFLD is associated with involvement of T cells and NK cells in mice.
Experimental Animal Facility, National Institute of Immunology, New Delhi - 100 067, India.
Jashdeep
J
Bhattacharjee
CSIR - Centre for Cellular and Molecular Biology, Hyderabad, India.
Jerald Mahesh
JM
Kumar
Experimental Animal Facility, National Institute of Immunology, New Delhi - 100 067, India.
Shailendra
S
Arindkar
Experimental Animal Facility, National Institute of Immunology, New Delhi - 100 067, India.
Barun
B
Das
Experimental Animal Facility, National Institute of Immunology, New Delhi - 100 067, India.
Upadhyay
U
Pramod
Experimental Animal Facility, National Institute of Immunology, New Delhi - 100 067, India.
Ramesh C
RC
Juyal
Experimental Animal Facility, National Institute of Immunology, New Delhi - 100 067, India.
Subeer S
SS
Majumdar
Experimental Animal Facility, National Institute of Immunology, New Delhi - 100 067, India. Electronic address: nagarajan@nii.ac.in.
Perumal
P
Nagarajan
D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000209:etiology*; D005434:Flow Cytometry; D005632:Fructose / Q000008:administration & dosage*; D005786:Gene Expression Regulation; D016867:Immunocompromised Host; D020287:In Situ Nick-End Labeling; D051379:Mice; D008819:Mice, Nude; D065626:Non-alcoholic Fatty Liver Disease; D016133:Polymerase Chain Reaction
D005632:Fructose
ALT; AST; B cells; CHO; Fructose; MCP-1; Mouse models; NAFLD; NASH; NK; NK cells; PBMC; SCD-1; SREBP-1c; T cells; TGY; TNFα; alanine aminotransferase; aspartate aminotransferase; cholesterol; monocyte attracting chemokines-1; natural killer cells; non-alcoholic steatohepatitis; p53; peripheral blood mononuclear cell; protein 53; stearoyl-CoA desaturase-1; sterol regulatory element-binding protein; tryglycerides; tumor necrosis factor alpha