Steatohepatitis induced by intragastric overfeeding in mice

Qing Gao Deng, Hongyun She, Jason H. Cheng, Samuel W. French, Dennis Koop, Shigang Xiong, Hidekazu Tsukamoto

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174 Citations (Scopus)

Abstract

Nonalcoholic steatohepatitis is prevalent among obese individuals with excessive caloric intake, insulin resistance, and type II diabetes. However, no animal models exist that recapitulate this important association. This study produced and characterized steatohepatitis (SH) caused by intragastric overfeeding in mice. C57BL/6, tumor necrosis factor (TNF) type I receptor-deficient, and genetically matched wild type mice were fed via an implanted gastrostomy tube a high-fat diet for 9 weeks in the increasing amount up to 85% in excess of the standard intake. Animals were examined for weight gain, insulin sensitivity, and histology and biochemistry of liver and white adipose tissue (WAT). Overfed C57BL/6 mice progressively became obese, with 71% larger final body weights. They had increased visceral WAT, hyperglycemia, hyperinsulinemia, hyperleptinemia, glucose intolerance, and insulin resistance. Of these mice, 46% developed SH with increased plasma alanine aminotransferase (121 ± 27 vs. 13 ± 1 U/L), neutrophilic infiltration, and sinusoidal and pericellular fibrosis. Obese WAT showed increased TNFα and leptin expression and reciprocally reduced adiponectin expression. The expression of lipogenic transcription factors (SREBP-1c, PPARγ, LXRα) was increased, whereas that of a lipolytic nuclear factor PPARα was reduced in SH. SH was associated with reduced cytochrome P450 (Cyp)2e1 but increased Cyp4a. TNF type I receptor deficiency did not prevent obesity and SH. In conclusion, forced overfeeding with a high-fat diet in mice induces obesity, insulin resistance, and SH in the absence of TNF signaling or Cyp2e1 induction.

Original languageEnglish (US)
Pages (from-to)905-914
Number of pages10
JournalHepatology
Volume42
Issue number4
DOIs
StatePublished - Oct 2005

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Fatty Liver
White Adipose Tissue
Insulin Resistance
Receptors, Tumor Necrosis Factor, Type I
Peroxisome Proliferator-Activated Receptors
High Fat Diet
Tumor Necrosis Factor-alpha
Obesity
Sterol Regulatory Element Binding Protein 1
Cytochrome P-450 CYP2E1
Gastrostomy
Glucose Intolerance
Intra-Abdominal Fat
Adiponectin
Hyperinsulinism
Leptin
Energy Intake
Alanine Transaminase
Inbred C57BL Mouse
Hyperglycemia

ASJC Scopus subject areas

  • Hepatology

Cite this

Deng, Q. G., She, H., Cheng, J. H., French, S. W., Koop, D., Xiong, S., & Tsukamoto, H. (2005). Steatohepatitis induced by intragastric overfeeding in mice. Hepatology, 42(4), 905-914. https://doi.org/10.1002/hep.20877

Steatohepatitis induced by intragastric overfeeding in mice. / Deng, Qing Gao; She, Hongyun; Cheng, Jason H.; French, Samuel W.; Koop, Dennis; Xiong, Shigang; Tsukamoto, Hidekazu.

In: Hepatology, Vol. 42, No. 4, 10.2005, p. 905-914.

Research output: Contribution to journalArticle

Deng, QG, She, H, Cheng, JH, French, SW, Koop, D, Xiong, S & Tsukamoto, H 2005, 'Steatohepatitis induced by intragastric overfeeding in mice', Hepatology, vol. 42, no. 4, pp. 905-914. https://doi.org/10.1002/hep.20877
Deng QG, She H, Cheng JH, French SW, Koop D, Xiong S et al. Steatohepatitis induced by intragastric overfeeding in mice. Hepatology. 2005 Oct;42(4):905-914. https://doi.org/10.1002/hep.20877
Deng, Qing Gao ; She, Hongyun ; Cheng, Jason H. ; French, Samuel W. ; Koop, Dennis ; Xiong, Shigang ; Tsukamoto, Hidekazu. / Steatohepatitis induced by intragastric overfeeding in mice. In: Hepatology. 2005 ; Vol. 42, No. 4. pp. 905-914.
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