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High-fructose corn syrup-induced hepatic dysfunction in rats: improving effect of resveratrol

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Abstract

Purpose

The increased consumption of high-fructose corn syrup (HFCS) may contribute to the worldwide epidemic of fatty liver. In this study, we have investigated whether HFCS intake (20 % beverages) influences lipid synthesis and accumulation in conjunction with insulin receptor substrate-1/2 (IRS-1; IRS-2), endothelial nitric oxide synthase (eNOS), sirtuin 1 (SIRT1) and inducible NOS (iNOS) expressions in liver of rats. Resveratrol was tested for its potential efficacy on changes induced by HFCS.

Methods

Animals were randomly divided into four groups as control, resveratrol, HFCS and resveratrol plus HFCS (resveratrol + HFCS). HFCS was given as 20 % solutions in drinking water. Feeding of all rats was maintained by a standard diet that enriched with or without resveratrol for 12 weeks.

Results

Dietary HFCS increased triglyceride content and caused mild microvesicular steatosis in association with up-regulation of fatty acid synthase and sterol regulatory element binding protein (SREBP)-1c in liver of rats. Moreover, HFCS feeding impaired hepatic expression levels of IRS-1, eNOS and SIRT1 mRNA/proteins, but did not change iNOS level. Resveratrol promoted IRS, eNOS and SIRT1, whereas suppressed SREBP-1c expression in rats fed with HFCS.

Conclusions

Resveratrol supplementation considerably restored hepatic changes induced by HFCS. The improvement of hepatic insulin signaling and activation of SIRT1 by resveratrol may be associated with decreased triglyceride content and expression levels of the lipogenic genes of the liver.

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Abbreviations

HFCS:

High-fructose corn syrup

NAFLD:

Non-alcoholic fatty liver disease

Res:

Resveratrol

IRS-1; IRS-2:

Insulin receptor substrate-1/2

eNOS:

Endothelial nitric oxide synthase

SIRT1:

Sirtuin 1

iNOS:

Inducible nitric oxide synthase

FASN:

Fatty acid synthase

SREBP:

Sterol regulatory element binding protein

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

PI3K:

Phosphatidylinositol 3-kinase

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

H&E:

Hematoxylin and eosin

ORO:

Oil Red O

TBST:

Tris buffer with NaCl–Tween

HRP:

Horseradish peroxidase

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Acknowledgments

This study was supported by grants from Gazi University Research Fund (BAP 02/2011-39 and 02/2012-48).

Conflict of interest

There is no conflict of interest to disclose for any of the authors.

Author information

Authors and Affiliations

  1. Department of Biology, Faculty of Science, Karamanoglu Mehmetbey University, Karaman, Turkey

    Gokhan Sadi

  2. Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, Ankara, Turkey

    Volkan Ergin & Adnan Menevse

  3. Department of Medical Pathology, Faculty of Medicine, Gazi University, Ankara, Turkey

    Guldal Yilmaz

  4. Department of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Turkey

    M. Bilgehan Pektas, O. Gokhan Yildirim & Fatma Akar

Authors
  1. Gokhan Sadi
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  2. Volkan Ergin
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  7. Fatma Akar
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Correspondence to Fatma Akar.

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Sadi, G., Ergin, V., Yilmaz, G. et al. High-fructose corn syrup-induced hepatic dysfunction in rats: improving effect of resveratrol. Eur J Nutr 54, 895–904 (2015). https://doi.org/10.1007/s00394-014-0765-1

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  • DOI: https://doi.org/10.1007/s00394-014-0765-1

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