Transgenic mice expressing nuclear sterol regulatory element-binding protein 1c in adipose tissue exhibit liver histology similar to nonalcoholic steatohepatitis.
Nonalcoholic steatohepatitis (NASH) is one of the life-threatening hepatic diseases associated with insulin resistance. Here we report that nuclear sterol regulatory element-binding protein 1c (nSREBP-1c) transgenic mice, an inherited lipodystrophic model with severe insulin resistance, spontaneously develop steatohepatitis. The animal had marked fatty liver accompanied by hyperglycemia, hypoleptinemia, and hypoadiponectinemia. Liver histology similar to NASH, that is, mononuclear cell infiltration, pericellular fibrosis, ballooning degeneration, and Mallory hyaline body formation were seen in the livers from transgenic mice 20 weeks or older. In contrast, no liver histologic abnormalities were noted in wild-type mice aged 30 weeks. Immunoreactive 8-hydroxy-2'-deoxyguanosine was observed in the nuclei of livers from transgenic mice, suggesting that in addition to insulin resistance, oxidative stress may be involved in the development of the NASH-like lesion. Thus, the nSREBP-1c transgenic mouse may serve as a unique model of spontaneously occurring NASH.
Nakayama
Hitomi
H
Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan.
Otabe
Shuichi
S
Ueno
Takato
T
Hirota
Naotoshi
N
Yuan
Xiaohong
X
Fukutani
Tomoka
T
Hashinaga
Toshihiko
T
Wada
Nobuhiko
N
Yamada
Kentaro
K
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism*; D017931:DNA Primers; D005234:Fatty Liver / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007333:Insulin Resistance; D008099:Liver / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*
D017931:DNA Primers; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1