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European Journal of Nutrition

, Volume 57, Issue 6, pp 2171–2187 | Cite as

Chronic consumption of fructose in combination with trans fatty acids but not with saturated fatty acids induces nonalcoholic steatohepatitis with fibrosis in rats

  • Sugeedha Jeyapal
  • Uday Kumar Putcha
  • Venkata Surekha Mullapudi
  • Sudip Ghosh
  • Anil Sakamuri
  • Suryam Reddy Kona
  • Sai Santosh Vadakattu
  • Chandana Madakasira
  • Ahamed IbrahimEmail author
Original Contribution

Abstract

Purpose

Consumption of Western diet high in fat and fructose has been attributed to the recent epidemic of nonalcoholic fatty liver disease (NAFLD). However, the impact of specific fatty acids on the progression of NAFLD to nonalcoholic steatohepatitis (NASH) is poorly understood. In the present study, we investigated the chronic effects of consumption of fructose in combination with saturated fatty acids (SFA) or trans fatty acids (TFA) on the development of NAFLD.

Methods

Male Sprague–Dawley rats were randomly assigned to six isocaloric starch/high fructose (44% of calories), high fat (39% calories) diet containing either starch–peanut oil, fructose–peanut oil, fructose–palmolein, fructose–clarified butter, fructose–coconut oil or fructose–partially hydrogenated vegetable oil and fed for 24 weeks. Palmolein, clarified butter and coconut oil were used as the source of SFA whereas partially hydrogenated vegetable oil was used as the source of TFA. Peanut oil was used as the reference oil.

Results

Long-term feeding of fructose in combination with SFA or TFA induced hepatic steatosis of similar extent associated with upregulation of stearoyl CoA desaturase-1. In contrast, fructose in combination with TFA induced NASH with fibrosis as evidenced by upregulation of hepatic proinflammatory cytokine and fibrogenic gene expression, increased hepatic oxidative stress and adipocytokine imbalance. Histopathological analysis revealed the presence of NASH with fibrosis. Further, peanut oil prevented the development of NAFLD in fructose-fed rats.

Conclusion

Fructose in combination with TFA caused NASH with fibrosis by inducing oxidative stress and inflammation, whereas, fructose in combination with SFA caused simple steatosis, suggesting that the type of fatty acid is more important for the progression of NAFLD.

Keywords

Western diet High fructose High fat Saturated fatty acids Trans fatty acids Inflammation Oxidative stress Gene expression Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis Fibrosis 

Abbreviations

ACC α

Acetyl CoA carboxylase alpha

ALT

Alanine aminotransferases

AST

Aspartate aminotransferases

AUC

Area under the curve

CB

Clarified butter

ChREBP

Carbohydrate responsive element binding protein

CO

Coconut oil

CPT 1

Carnitine palmotyl tranferase 1

ELISA

Enzyme linked immunosorbent assay

FAME

Fatty acid methyl ester

FAS

Fatty acid synthase

FR-PNO

Fructose–peanut oil

FR-PO

Fructose–palmolein

FR-CB

Fructose–clarified butter

FR-CO

Fructose–coconut oil

FR-PHVO

Fructose–partially hydrogenated vegetable oil

GPx

Glutathione peroxidase

GSH

Reduced glutathione

H&E

Hematoxylin and eosin

HDL

High-density lipoprotein

HOMA-IR

Homeostasis model assessment-insulin resistance

HSC

Hepatic stellate cells

IL-1β

Interleukin-1 beta

IL-6

Interleukin-6

IPGTT

Intraperitoneal glucose tolerance test

NAFLD

Nonalcoholic fatty liver disease

NAS

NAFLD Activity score

NASH

Nonalcoholic steatohepatitis

PAI-1

Plasminogen activator inhibitor-1

PCR

Polymerase chain reaction

PHVO

Partially hydrogenated vegetable oil

PNO

Peanut oil

PO

Palmolein

PPAR α

Peroxisome proliferator-activated receptor alpha

PPAR γ

Peroxisome proliferator-activated receptor gamma

SCD-1

Stearoyl CoA desaturase-1

SFA

Saturated fatty acid

SOD

Superoxide dismutase

SREBP 1c

Sterol regulatory element binding protein 1c

TBARS

Thiobarbituric acid reactive substances

TFA

Trans fatty acid

TNF α

Tumor necrosis factor alpha

Notes

Acknowledgements

This study was funded by Grants in aid (5/4/3-7/TF/2011/NCD-II) from Indian Council of Medical Research, Government of India to AI. JS was supported by a fellowship from Indian Council of Medical Research, Government of India.

Author contributions

AI and JS designed the study, analyzed the data and wrote the manuscript. JS, AS, KSR and VSS conducted the animal experiment and prepared the experimental diets. PUK and MVS carried out histopathological analysis of liver and NAS scoring. SG and JS involved in mRNA expression studies by RT-qPCR. JS, KSR and CM carried out biochemical estimations. All the authors read and approved the manuscript.

Compliance with ethical standards

Conflict of interest

All the authors declare no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Sugeedha Jeyapal
    • 1
  • Uday Kumar Putcha
    • 2
  • Venkata Surekha Mullapudi
    • 2
  • Sudip Ghosh
    • 3
  • Anil Sakamuri
    • 1
  • Suryam Reddy Kona
    • 1
  • Sai Santosh Vadakattu
    • 1
  • Chandana Madakasira
    • 1
  • Ahamed Ibrahim
    • 1
    Email author
  1. 1.Department of Lipid ChemistryNational Institute of NutritionHyderabadIndia
  2. 2.Department of PathologyNational Institute of NutritionHyderabadIndia
  3. 3.Department of Molecular BiologyNational Institute of NutritionHyderabadIndia

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