The effect of high-fat diet and 13-cis retinoic acid application on lipid profile, glycemic response and oxidative stress in female Lewis rats

PLoS One. 2020 Sep 18;15(9):e0238600. doi: 10.1371/journal.pone.0238600. eCollection 2020.


Vitamin A and its metabolites are key regulators of the development of adipose tissue and associated metabolic complications. The aim of this study was to determine the effect of high fat diet and 13-cis retinoic acid (13 cRA) application on metabolic parameters, adipogenic and inflammatory indicators in female Lewis rats. Female rats of Lewis strain were fed standard laboratory diet (STD) and high fat diet (HFD, 45% of saturated fatty acids) during 30 days. The groups were divided into additional 3 groups (6 rats each): two experimental groups that received 13 cRA orally on a daily basis during 30 days (7.5 mg/kg and 15 mg/kg, respectively) and the control group that was given sunflower oil. Animals were sacrificed after 60 days. Feeding of Lewis rats with chronic HFD diet with 13 cRA supplementation increased weight gain, adiposity index, dyslipidaemia, hyperleptinaemia, insulin resistance, VLDL concentrations, oxidative stress and atherogenic indices. Administration of 13 cRA in Lewis rats fed STD did not change the weight of the animals, but it slightly increased the atherogenic parameters. 13 cRA and HFD affect metabolic parameters, glucose and lipid metabolism in Lewis rats and its administration has a completely different effect on metabolism in rats fed STD, highlighting the complex role of vitamin A supplementation in obesity. Other factors, such as genetics, age, sex, adipose tissue distribution, also must be taken into consideration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis / drug effects
  • Animals
  • Diet, High-Fat*
  • Female
  • Glucose / metabolism*
  • Insulin Resistance
  • Isotretinoin / administration & dosage
  • Isotretinoin / pharmacology*
  • Lipid Metabolism / drug effects*
  • Obesity / metabolism
  • Oxidative Stress / drug effects*
  • Rats, Inbred Lew
  • Weight Gain / drug effects


  • Isotretinoin
  • Glucose

Grant support

This work was supported in part by Faculty of Dental Medicine and Health under grants ID: VIF-2018- FDMZOS-O4 and ID: IP1 2019. There was no additional external funding received for this study. Faculty of Dental Medicine and Health did not play any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.