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Genetic differences in oxidative stress and inflammatory responses to diet-induced obesity do not alter liver fibrosis in mice.

Publication ,  Journal Article
Syn, W-K; Yang, L; Chiang, DJ; Qian, Y; Jung, Y; Karaca, G; Choi, SS; Witek, RP; Omenetti, A; Pereira, TA; Diehl, AM
Published in: Liver Int
September 2009

OBJECTIVE: To determine how genetic factors might influence the progression of nonalcoholic fatty liver disease (NAFLD). DESIGN/INTERVENTION: Beginning in adolescence, male C57BL6 (BL6) and 129/SVJ mice were fed control (n=15/group) or high-fat (HF) diets (n=30/group) for 6 months. MAIN OUTCOME MEASURES: Assessed were body weight, insulin resistance, hepatic production of free radicals, expression of cytokines and fibrosis-related genes and severity of hepatic steatosis, injury and fibrosis. RESULTS: High-fat diets induced comparable obesity, hepatic steatosis and insulin resistance in the two strains. Compared with BL6 mice, 129/SVJ mice had impaired induction of antioxidant genes, generated three- to four-fold more free radicals and exhibited two-fold greater induction of profibrogenic cytokines (interleukin-4 and transforming growth factor-beta1) and fibrosis-related genes (fibronectin and tissue inhibitor of metalloproteinase-1) (all P<0.05 for 129 vs BL6). Surprisingly, however, induction of collagen I alpha1 mRNA and accumulation of Sirius red-stained fibrils and hepatic hydroxyproline were similar in BL6 and 129/SVJ mice, and although patchy sinusoidal fibrosis emerged in both strains, neither developed bridging fibrosis. CONCLUSIONS: Although BL6 and 129/SVJ mice with diet-induced obesity, insulin resistance and steatosis differed with respect to several factors that are thought to influence human NAFLD progression, they developed comparable liver fibrosis. Moreover, none of the risk factors for NAFLD-related cirrhosis in humans, including obesity, insulin resistance, chronic inflammatory and oxidant stress, steatohepatitis or activation of fibrogenic genes, proved to be sufficient to cause cirrhosis in these mice, even when exposure to one or more of these insults was very prolonged.

Duke Scholars

Published In

Liver Int

DOI

EISSN

1478-3231

Publication Date

September 2009

Volume

29

Issue

8

Start / End Page

1262 / 1272

Location

United States

Related Subject Headings

  • Species Specificity
  • RNA, Messenger
  • Oxidative Stress
  • Obesity
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Liver Function Tests
  • Liver Cirrhosis
  • Genetic Predisposition to Disease
 

Citation

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Syn, W.-K., Yang, L., Chiang, D. J., Qian, Y., Jung, Y., Karaca, G., … Diehl, A. M. (2009). Genetic differences in oxidative stress and inflammatory responses to diet-induced obesity do not alter liver fibrosis in mice. Liver Int, 29(8), 1262–1272. https://doi.org/10.1111/j.1478-3231.2009.02036.x
Syn, Wing-Kin, Liu Yang, Dian Jung Chiang, Yue Qian, Youngmi Jung, Gamze Karaca, Steve S. Choi, et al. “Genetic differences in oxidative stress and inflammatory responses to diet-induced obesity do not alter liver fibrosis in mice.Liver Int 29, no. 8 (September 2009): 1262–72. https://doi.org/10.1111/j.1478-3231.2009.02036.x.
Syn W-K, Yang L, Chiang DJ, Qian Y, Jung Y, Karaca G, et al. Genetic differences in oxidative stress and inflammatory responses to diet-induced obesity do not alter liver fibrosis in mice. Liver Int. 2009 Sep;29(8):1262–72.
Syn, Wing-Kin, et al. “Genetic differences in oxidative stress and inflammatory responses to diet-induced obesity do not alter liver fibrosis in mice.Liver Int, vol. 29, no. 8, Sept. 2009, pp. 1262–72. Pubmed, doi:10.1111/j.1478-3231.2009.02036.x.
Syn W-K, Yang L, Chiang DJ, Qian Y, Jung Y, Karaca G, Choi SS, Witek RP, Omenetti A, Pereira TA, Diehl AM. Genetic differences in oxidative stress and inflammatory responses to diet-induced obesity do not alter liver fibrosis in mice. Liver Int. 2009 Sep;29(8):1262–1272.
Journal cover image

Published In

Liver Int

DOI

EISSN

1478-3231

Publication Date

September 2009

Volume

29

Issue

8

Start / End Page

1262 / 1272

Location

United States

Related Subject Headings

  • Species Specificity
  • RNA, Messenger
  • Oxidative Stress
  • Obesity
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Liver Function Tests
  • Liver Cirrhosis
  • Genetic Predisposition to Disease