title: Involvement of splenic iron accumulation in the development of nonalcoholic steatohepatitis in Tsumura Suzuki Obese Diabetes mice.
abstract: Nonalcoholic steatohepatitis (NASH) is a common hepatic manifestation of metabolic syndrome and can lead to hepatic cirrhosis and cancer. It is considered that NASH is caused by multiple parallel events, including abnormal lipid metabolism, gut-derived-endotoxin-induced inflammation, and adipocytokines derived from adipose tissue, suggesting that other tissues are involved in NASH development. Previous studies demonstrated that spleen enlargement is observed during the course of NASH pathogenesis. However, the involvement of splenic status in the progression of NASH remains unclear. In this study, we examined hepatic and splenic histopathological findings in the early stage of NASH using the Tsumura Suzuki Obese Diabetes (TSOD) mouse model established for assessing NASH. We found that 12-week-old TSOD mice clearly exhibited the histopathological features of NASH in the early stage. At this age, the spleen of TSOD mice showed markedly higher iron level than that of control Tsumura Suzuki Non Obesity (TSNO) mice. The level of accumulated iron was significantly decreased by feeding a diet with glucosyl hesperidin, a bioactive flavonoid, accompanied with alleviation of hepatic lesions. Furthermore, we found that splenic iron level was positively correlated with the severity of NASH manifestations, suggesting that abnormalities in the spleen are involved in the development of NASH.
authors.affiliation: Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Takamatsu, Kagawa 761-0395, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Murotomi
authors.affiliation: Hayashibara Co., Ltd., Naka-ku, Okayama 702-8006, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Arai
authors.affiliation: Hayashibara Co., Ltd., Naka-ku, Okayama 702-8006, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Uchida
authors.affiliation: Hayashibara Co., Ltd., Naka-ku, Okayama 702-8006, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Endo
authors.affiliation: Hayashibara Co., Ltd., Naka-ku, Okayama 702-8006, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Mitsuzumi
authors.affiliation: Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Takamatsu, Kagawa 761-0395, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Tabei
authors.affiliation: Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Takamatsu, Kagawa 761-0395, Japan.
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Takamatsu, Kagawa 761-0395, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nakajima
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004195:Disease Models, Animal; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000378:metabolism*; D009765:Obesity / Q000150:complications*; D013154:Spleen / Q000378:metabolism*
chemical_list: D007501:Iron