Tags

Type your tag names separated by a space and hit enter

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.LI

Abstract

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.

Authors+Show Affiliations

Department of Medicine, Division of Gastroenterology, Duke University Medical Center, Durham, NC 27710, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

19490416

Citation

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 International : Official Journal of the International Association for the Study of the Liver, vol. 29, no. 8, 2009, pp. 1262-72.
Syn WK, Yang L, Chiang DJ, et al. Genetic differences in oxidative stress and inflammatory responses to diet-induced obesity do not alter liver fibrosis in mice. Liver Int. 2009;29(8):1262-72.
Syn, W. K., Yang, L., Chiang, D. J., Qian, Y., Jung, Y., Karaca, G., Choi, S. S., Witek, R. P., Omenetti, A., Pereira, T. A., & Diehl, A. M. (2009). Genetic differences in oxidative stress and inflammatory responses to diet-induced obesity do not alter liver fibrosis in mice. Liver International : Official Journal of the International Association for the Study of the Liver, 29(8), 1262-72. https://doi.org/10.1111/j.1478-3231.2009.02036.x
Syn WK, et al. Genetic Differences in Oxidative Stress and Inflammatory Responses to Diet-induced Obesity Do Not Alter Liver Fibrosis in Mice. Liver Int. 2009;29(8):1262-72. PubMed PMID: 19490416.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic differences in oxidative stress and inflammatory responses to diet-induced obesity do not alter liver fibrosis in mice. AU - Syn,Wing-Kin, AU - Yang,Liu, AU - Chiang,Dian Jung, AU - Qian,Yue, AU - Jung,Youngmi, AU - Karaca,Gamze, AU - Choi,Steve S, AU - Witek,Rafal P, AU - Omenetti,Alessia, AU - Pereira,Thiago A, AU - Diehl,Anna Mae, Y1 - 2009/04/20/ PY - 2009/6/4/entrez PY - 2009/6/6/pubmed PY - 2009/10/21/medline SP - 1262 EP - 72 JF - Liver international : official journal of the International Association for the Study of the Liver JO - Liver Int. VL - 29 IS - 8 N2 - 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. SN - 1478-3231 UR - https://www.unboundmedicine.com/medline/citation/19490416/Genetic_differences_in_oxidative_stress_and_inflammatory_responses_to_diet_induced_obesity_do_not_alter_liver_fibrosis_in_mice_ L2 - https://doi.org/10.1111/j.1478-3231.2009.02036.x DB - PRIME DP - Unbound Medicine ER -