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Genome-wide transcriptome expression in the liver of a mouse model of high carbohydrate diet-induced liver steatosis and its significance for the disease

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Abstract

Purpose

To perform a large-scale gene profiling of the liver in a mouse model of fatty liver induced by high carbohydrate (sucrose) diet (HCD) to gain a deeper insight into potential mechanisms of diet-induced hepatic steatosis.

Methods

C57BL/6 male mice were fed either a purified, control diet or a HCD for 16 weeks. HCD feeding led to marked liver steatosis without inflammation or necrosis. The expression of 42,500 genes/sequences was assessed.

Results

A number of genes (471) underwent significant expression changes in HCD- as compared to standard diet-fed mice (n = 5/group; P < 0.01). Of these genes, 211 were down- and 260 up-regulated. The latter group includes 20 genes encoding enzymes involved in carbohydrate conversion to fat. The genes that underwent expression changes perform a large variety of molecular functions, and the vast majority of these have never been tested before in non-alcoholic fatty liver of nutritional origin. They reveal novel aspects of the disease and allow identification of candidate genes that may underlie the initiation of hepatic steatosis and progression to non-alcoholic steatohepatitis.

Conclusions

HCD-fed laboratory animals provide a model of early non-alcoholic fatty liver disease resembling the disease in humans. The genome wide gene profiling of the liver reveals the complexity of the disease, unravels novel aspects of HCD-induced hepatic steatosis, and helps elucidate its nature and mechanisms.

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Abbreviations

ALT:

Alanine-2-oxoglutarate amino transferase (EC 2.6.1.2)

HCD:

High-carbohydrate diet

NAFLD:

Nonalcoholic fatty liver disease

NASH:

Nonalcoholic steatohepatitis

TBARS:

Thiobarbituric acid reactive substances

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Acknowledgements

The work reported in this study was supported by National Institutes of Health grants (to I.V.D., Z.S., S.S.B., T.B.K., A.V.S., and C.J.M.) and a Department of Veterans Affairs grant (to C.J.M.).

Author information

Authors and Affiliations

  1. Division of Gastroenterology/Hepatology, Department of Medicine, University of Louisville School of Medicine, 550 S. Jackson Street, ACB Bldg., Third Floor, Louisville, KY, 40202, USA

    Ion V. Deaciuc, Zhenyuan Song, Shirish S. Barve, Ming Song & Craig J. McClain

  2. Biometrics and Data Management Department, Takeda Global Research and Development Center, Inc., Lincolnshire, IL, 60069, USA

    Xuejun Peng

  3. Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, 40202, USA

    Shirish S. Barve & Craig J. McClain

  4. Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY, 40202, USA

    Qiang He

  5. Department of Molecular, Cellular and Craniofacial Biology, University of Louisville, Louisville, KY, 40202, USA

    Thomas B. Knudsen & Amar V. Singh

  6. Louisville Veterans Administration Medical Center, Louisville, KY, 40202, USA

    Craig J. McClain

Authors
  1. Ion V. Deaciuc
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  2. Zhenyuan Song
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  3. Xuejun Peng
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  4. Shirish S. Barve
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  5. Ming Song
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  6. Qiang He
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  7. Thomas B. Knudsen
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  8. Amar V. Singh
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  9. Craig J. McClain
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Corresponding author

Correspondence to Ion V. Deaciuc.

Additional information

Ion V. Deaciuc and Zhenyuan Song are contributed equally to this study.

Electronic supplementary material

Below are the link to the electronic supplementary material. Two tables (Microsoft Excel), one comprising all the genes that underwent changes in their expression with statistical processing and another comprising gene ontology for the genes involved in carbohydrate and lipid metabolism.

ESM1 (XLS 948 kb)

ESM2 (XLS 27 kb)

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Deaciuc, I.V., Song, Z., Peng, X. et al. Genome-wide transcriptome expression in the liver of a mouse model of high carbohydrate diet-induced liver steatosis and its significance for the disease. Hepatol Int 2, 39–49 (2008). https://doi.org/10.1007/s12072-007-9025-2

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  • DOI: https://doi.org/10.1007/s12072-007-9025-2

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