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Dietary fructose exacerbates hepatocellular injury when incorporated into a methionine-choline-deficient diet

Authors

  • Michael K. Pickens,

    1. Department of Pediatrics, University of California, San Francisco, CA, USA
    2. The Liver Center, University of California, San Francisco, CA, USA
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  • Hisanobu Ogata,

    1. The Liver Center, University of California, San Francisco, CA, USA
    2. Department of Internal Medicine, University of California, San Francisco, CA, USA
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  • Russell K. Soon,

    1. The Liver Center, University of California, San Francisco, CA, USA
    2. Department of Internal Medicine, University of California, San Francisco, CA, USA
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  • James P. Grenert,

    1. The Liver Center, University of California, San Francisco, CA, USA
    2. Department of Pathology, University of California, San Francisco, CA, USA
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  • Jacquelyn J. Maher

    1. The Liver Center, University of California, San Francisco, CA, USA
    2. Department of Internal Medicine, University of California, San Francisco, CA, USA
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Correspondence
Jacquelyn J. Maher, MD, Rice Liver Center Laboratory, San Francisco General Hospital, Bldg 40, Room 4102, 1001 Potrero Avenue, San Francisco, CA 94110, USA
Tel: +1 415 206 4805
Fax: +1 415 641 0517
e-mail:jmaher@medsfgh.ucsf.edu

Abstract

Background: Methionine-choline-deficient (MCD) diets cause steatohepatitis in rodents and are used to model fatty liver disease in human beings. Recent studies have identified sucrose as a major contributor to MCD-related liver disease through its ability to promote hepatic de novo lipogenesis.

Aims: To determine whether glucose and fructose, the two constitutents of sucrose, differ in their capacity to provoke steatohepatitis when incorporated individually into MCD formulas.

Materials & Methods: MCD and control formulas prepared with either glucose or fructose as the sole source of carbohydrate were fed to mice for 21 days. Liver injury was assessed biochemically and histologically together with hepatic gene expression and fatty acid analysis.

Results: Mice fed MCD formulas developed similar degrees of hepatic steatosis whether they contained glucose or fructose. By contrast, mice fed MCD-fructose developed significantly more hepatocellular injury than mice fed MCD-glucose, judged by histology, apoptosis staining and serum alanine aminotransferase. Liver injury in MCD-fructose mice coincided with an exaggerated rise in the ratio of long-chain saturated to unsaturated fatty acids in the liver. Notably, hepatic inflammation was not enhanced in mice fed MCD-fructose, correlating instead with hepatic lipid peroxidation, which was equivalent in the two MCD groups.

Discussion: Fructose is more cytotoxic than glucose when used as the source of carbohydrate in MCD formulas.

Conclusion: The data suggest the enhanced cytotoxicity of fructose in the MCD model is related to its ability to stimulate de novo lipogenesis, which yields harmful long-chain saturated fatty acids.

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