Partially hydrogenated vegetable oil containing 5% trans fats when combined with fructose exacerbates obesity and non-alcoholic fatty liver disease in rats



The aim of this study is to test the hypothesis that feeding trans fatty acids (TFA) (5%) along with fructose exacerbates obesity and non-alcoholic fatty liver disease (NAFLD) in rats.


Male Wistar rats were randomized into four groups, i.e., standard diet, 5% TFA + standard diet, fructose + standard diet, and TFA + fructose + standard diet. All the diets were provided for 16 weeks. The body weight, body mass index, calorie intake, adiposity index, and liver index were determined. Serum glucose, insulin, lipid profile, and liver enzymes were estimated. Liver lipids, markers of oxidative stress, inflammation, and collagen were estimated in the liver. The histopathological evaluation of the adipose tissue and liver were carried out.


TFA + standard diet caused an increase in body weight while TFA + fructose + standard diet caused significant body weight gain, adiposity index, and hypertrophy of adipocytes. TFA + fructose + standard diet caused insulin resistance and dyslipidemia in the rats. Rats in the TFA + standard diet group showed marked hepatic steatosis and an elevation in alanine aminotransferase, while those in the TFA + fructose + standard diet group showed oxidative stress, inflammation, and fibrosis in the liver.


Feeding of TFA at a concentration of 5% along with the standard diet resulted in an increase in the body weight and hepatic steatosis, but the addition of fructose to 5% TFA and standard diet resulted in obesity and non-alcoholic steatohepatitis. Thus, the reduction in TFA content of foods must be accompanied by a significant decrease in the fructose intake in order to protect against obesity and NAFLD.

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Fig. 1
Fig. 2



ratio-abdominal circumference to thoracic circumference ratio


alkaline phosphatase


alanine aminotransferase


aspartate aminotransferase


body mass index


gamma-glutamyl transferase


reduced glutathione


high density lipoprotein cholesterol


homeostasis model assessment-insulin resistance


low density lipoprotein cholesterol




non-alcoholic fatty liver disease


nonalcoholic steatohepatitis


partially hydrogenated vegetable oil


superoxide dismutase


trans fatty acids




very low density lipoprotein cholesterol


World Health Organization


  1. 1.

    Drewnowski A. The real contribution of added sugars and fats to obesity. Epidemiol Rev. 2007;29:160–71.

    Article  Google Scholar 

  2. 2.

    WHO calls on countries to reduce sugars intake among adults and children. Available at Accessed 11 June 2019.

  3. 3.

    Walker RW, Dumke KA, Goran MI. Fructose content in popular beverages made with and without high-fructose corn syrup. Nutrition. 2014;30:928–35.

    CAS  Article  Google Scholar 

  4. 4.

    Dornas WC, de Lima WG, Pedrosa ML, Silva ME. Health implications of high-fructose intake and current research. Adv Nutr. 2015;6:729–37.

    CAS  Article  Google Scholar 

  5. 5.

    Bhardwaj S, Passi SJ, Misra A. Overview of trans fatty acids: biochemistry and health effects. Diabetes Metab Syndr. 2011;5:161–4.

    Article  Google Scholar 

  6. 6.

    Micha R, Khatibzadeh S, Shi P, Fahimi S, Lim S, Andrews KG, et al. Global, regional, and national consumption levels of dietary fats and oils in 1990 and 2010: a systematic analysis including 266 country-specific nutrition surveys. BMJ. 2014;348:g2272.

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Brownell KD, Pomeranz JL. The trans-fat ban-food regulation and long term health. N Engl J Med. 2014;370:1773–5.

    CAS  Article  Google Scholar 

  8. 8.

    WHO plan to eliminate industrially-produced trans-fatty acids from global food supply. Available from Accessed 16 August 2018.

  9. 9.

    FSSAI launches new campaign to eliminate trans fats by 2022. Available from Accessed 15 December 2018.

  10. 10.

    Koppe SW, Elias M, Moseley RH, Green RM. Trans fat feeding results in higher serum alanine aminotransferase and increased insulin resistance compared with a standard murine high-fat diet. Am J Physiol Gastrointest Liver Physiol. 2009;297:G378–84.

    CAS  Article  Google Scholar 

  11. 11.

    Jeyapal S, Putcha UK, Mullapudi VS, Ghosh S, Sakamuri A, Kona SR, et al. Chronic consumption of fructose in combination with trans fatty acids but not with saturated fatty acids induces non-alcoholic steatohepatitis with fibrosis in rats. Eur J Nutr. 2018;57:2171–87.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    de Lima VM, Oliveira CP, Alves VA, Chammas MC, Oliveira EP, Stefano JT, et al. A rodent model of NASH with cirrhosis, oval cell proliferation and hepatocellular carcinoma. J Hepatol. 2008;49:1055–61.

    Article  Google Scholar 

  13. 13.

    Zhao X, Shen C, Zhu H, Wang C, Liu X, Sun X, et al. Trans-fatty acids aggravate obesity, insulin resistance and hepatic steatosis in C57BL/6 mice, possibly by suppressing the IRS1 dependent pathway Molecules 2016;21(6). pii:E705. doi:

  14. 14.

    Machado RM, Stefano JT, Oliveira CP, Mello ES, Ferreira FD, Nunes VS, et al. Intake of trans fatty acids causes nonalcoholic steatohepatitis and reduces adipose tissue fat content. J Nutr. 2010;140:1127–32.

    CAS  Article  Google Scholar 

  15. 15.

    Obara N, Fukushima K, Ueno Y, Wakui Y, Kimura O, Tamai K, et al. Possible involvement and the mechanisms of excess trans-fatty acid consumption in severe NAFLD in mice. J Hepatol. 2010;53:326–34.

    CAS  Article  Google Scholar 

  16. 16.

    Fakhoury-Sayegh N, Trak-Smayra V, Sayegh R, Haidar F, Obeid O, Asmar S, et al. Fructose threshold for inducing organ damage in a rat model of non-alcoholic fatty liver disease. Nutr Res. 2019;62:101–12.

    CAS  Article  Google Scholar 

  17. 17.

    Novelli EL, Diniz YS, Galhardi CM, Ebaid GM, Rodrigues HG, Mani F, et al. Anthropometrical parameters and markers of obesity in rats. Lab Anim. 2007;41:111–9.

    CAS  Article  Google Scholar 

  18. 18.

    Adorni CS, Corrêa CR, Vileigas DF, de Campos DH, Padovani CR, Minatel IO, et al. The influence of obesity by a diet high in saturated fats and carbohydrates balance in the manifestation of systemic complications and comorbidities. Nutrire. 2017;42(1):16.

    Article  Google Scholar 

  19. 19.

    Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care. 2004;27:1487–95.

    Article  Google Scholar 

  20. 20.

    Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499–502.

    CAS  Article  Google Scholar 

  21. 21.

    Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem. 1957;226:497–509.

    CAS  Google Scholar 

  22. 22.

    Lo AT, Francisqueti FV, Hasimoto FK, Ferraz AP, Minatel IO, Garcia JL, et al. Brazilian Curcuma longa L. attenuates comorbidities by modulating adipose tissue dysfunction in obese rats. Nutrire. 2018;43(1):25.

    CAS  Article  Google Scholar 

  23. 23.

    Neuman RE, Logan MA. The determination of hydroxyproline. J Biol Chem. 1950;184:299–306.

    CAS  PubMed  Google Scholar 

  24. 24.

    Pai SA, Majumdar AS. Protective effects of melatonin against metabolic and reproductive disturbances in polycycstic ovary syndrome in rats. J Pharm Pharmacol. 2014;66:1710–21.

    CAS  Article  Google Scholar 

  25. 25.

    Kismet K, Ozcan C, Kuru S, Gencay Celemli O, Celepli P, Senes M, et al. Does propolis have any effect on non-alcoholic fatty liver disease? Biomed Pharmacother. 2017;90:863–71.

    CAS  Article  Google Scholar 

  26. 26.

    Mattes R, Foster GD. Food environment and obesity. Obesity. 2014;22:2459–61.

    PubMed  Google Scholar 

  27. 27.

    Lindqvist A, Baelemans A, Erlanson-Albertsson C. Effects of sucrose, glucose and fructose on peripheral and central appetite signals. Regul Pept. 2008;150:26–32.

    CAS  Article  Google Scholar 

  28. 28.

    Longhi R, Almeida RF, Machado L, Duarte MM, Souza DG, Machado P, et al. Effect of a trans fatty acid-enriched diet on biochemical and inflammatory parameters in Wistar rats. Eur J Nutr. 2017;56:1003–16.

    CAS  Article  Google Scholar 

  29. 29.

    Mazidi M, Katsiki N, Mikhailidis DP, Banach M. Link between plasma trans-fatty acid and fatty liver is moderated by adiposity. Int J Cardiol. 2018;272:316–22.

    Article  Google Scholar 

  30. 30.

    Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism. 2016;65:1038–48.

    CAS  Article  Google Scholar 

  31. 31.

    Dhibi M, Brahmi F, Mnari A, Houas Z, Charqui I, Bchir L, et al. The intake of high fat diet with different trans fatty acid levels differentially induces oxidative stress and non alcoholic fatty liver disease (NAFLD) in rats. Nutr Metab. 2011;8:65.

    CAS  Article  Google Scholar 

  32. 32.

    Mraz M, Haluzik M. The role of adipose tissue immune cells in obesity and low-grade inflammation. J Endocrinol. 2014;222:R113–27.

    CAS  Article  Google Scholar 

  33. 33.

    Bhardwaj S, Passi SJ, Misra A, Pant KK, Anwar K, et al. Effect of heating/reheating of fats/oils, as used by Asian Indians, on trans fatty acid formation. Food Chem. 2016;212:663–70.

    CAS  Article  Google Scholar 

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The authors are grateful to Ms. Deepali Ganachari and Ms. Jaya Verma, research fellows at Dept. of Clinical Pharmacology, T.N. Medical College and BYL Nair Hospital for their help during animal experimentation, and Dr. Sanjay Pawar, veterinary pathologist for carrying out the histopathological evaluation of the liver and adipose tissue.


The University Grants Commission (BSR Fellowship), New Delhi, India, letter no. F.25–1/2014–15 (BSR)/No. F.5–63/2007 (BSR) dated 16 Feb 2015 is awarded to Ms. Sarayu Pai.

Author information




SAP carried out the experiments and wrote the first draft of the manuscript. RPM helped in designing the study and analyzing the data. ARJ was involved in designing the study and supervision of the conduct of the work. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Archana R. Juvekar.

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Ethics approval

The protocol was approved by the Institutional Animal Ethics Committee of T N Medical College and BYL Nair Charitable Hospital, Mumbai, India (protocol no. IAEC/2016/8 dated 29 February 2016).

Conflict of interest

The authors declare that they have no conflict of interests.

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Pai, S.A., Munshi, R.P. & Juvekar, A.R. Partially hydrogenated vegetable oil containing 5% trans fats when combined with fructose exacerbates obesity and non-alcoholic fatty liver disease in rats. Nutrire 45, 5 (2020).

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  • Fructose
  • Non-alcoholic fatty liver disease
  • Rats
  • Trans fatty acids