A novel animal model of nonalcoholic steatohepatitis (NASH)

Hypoxemia enhances the development of NASH

Fusako Takayama, Toru Egashira, Hiromu Kawasaki, Mitsumasa Mankura, Kazuo Nakamoto, Shigeru Okada, Akitane Mori

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Recent reports described a high incidence of nonalcoholic steatohepatitis (NASH) in patients with obstructive sleep apnea. Accordingly, we hypothesized that recurrent and intermittent hypoxemia plays an important role in the pathogenesis of NASH. Our objective was construction of a practical and accurate experimental model to reproduce the key features of NASH in humans. Chemical hypoxemia through methemoglobinemia was induced by daily intraperitoneal injection of sodium nitrite (40 mg/kg) for 4 weeks in rats with fatty liver. The later was induced by 4-week feeding a choline-deficient high-fat diet (CDHF). Besides, the normal chow diets feeding groups were prepared with in the same manner except for CDHF feeding. The animal experiment was performed in four groups; Normal control, Hypoxemia, CDHF, and CDHF + hypoxemia. Nitrite was given for the later 4 weeks to each rat of Hypoxemia and CDHF + hypoxemia. CDHF + hypoxemia rats were confirmed to develop histological changes that resemble those of patients with NASH, together with biochemical liver dysfunction, while CDHF group was limited in mild steatosis, and Hypoxemia group liver was normal. Present study established a reproducible and useful NASH model resembling the main features of NASH in humans, and showed first that recurrent and intermittent hypoxemia aggravate fatty liver to steatohepatitis and liver fibrosis.

Original languageEnglish
Pages (from-to)335-340
Number of pages6
JournalJournal of Clinical Biochemistry and Nutrition
Volume45
Issue number3
DOIs
Publication statusPublished - Nov 2009

Fingerprint

Nutrition
Choline
High Fat Diet
Animals
Animal Models
Fats
Liver
Fatty Liver
Rats
Sodium Nitrite
Methemoglobinemia
Hypoxia
Non-alcoholic Fatty Liver Disease
Nitrites
Obstructive Sleep Apnea
Intraperitoneal Injections
Liver Cirrhosis
Liver Diseases
Theoretical Models
Diet

Keywords

  • Hypoxemia
  • Methemoglobinemia
  • Obstructive sleep apnea
  • Oxidative stress

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

A novel animal model of nonalcoholic steatohepatitis (NASH) : Hypoxemia enhances the development of NASH. / Takayama, Fusako; Egashira, Toru; Kawasaki, Hiromu; Mankura, Mitsumasa; Nakamoto, Kazuo; Okada, Shigeru; Mori, Akitane.

In: Journal of Clinical Biochemistry and Nutrition, Vol. 45, No. 3, 11.2009, p. 335-340.

Research output: Contribution to journalArticle

Takayama, Fusako ; Egashira, Toru ; Kawasaki, Hiromu ; Mankura, Mitsumasa ; Nakamoto, Kazuo ; Okada, Shigeru ; Mori, Akitane. / A novel animal model of nonalcoholic steatohepatitis (NASH) : Hypoxemia enhances the development of NASH. In: Journal of Clinical Biochemistry and Nutrition. 2009 ; Vol. 45, No. 3. pp. 335-340.
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