Stevia-derived compounds attenuate the toxic effects of ectopic lipid accumulation in the liver of obese mice: a transcriptomic and metabolomic study

Food Chem Toxicol. 2015 Mar;77:22-33. doi: 10.1016/j.fct.2014.12.017. Epub 2014 Dec 29.


There is a close interaction between Type 2 Diabetes, obesity and liver disease. We have studied the effects of the two most abundant Stevia-derived steviol glycosides, stevioside and rebaudioside A, and their aglycol derivative steviol on liver steatosis and the hepatic effects of lipotoxicity using a mouse model of obesity and insulin resistance. We treated ob/ob and LDLR-double deficient mice with stevioside (10 mg⋅kg(-1)⋅day-1 p.o., n = 8), rebaudioside A (12 mg⋅kg(-1)⋅day-1 p.o., n = 8), or steviol (5 mg⋅kg(-1)⋅day(-1) p.o., n = 8). We determined their effects on liver steatosis and on the metabolic effects of lipotoxicity by histological analysis, and by combined gene-expression and metabolomic analyses. All compounds attenuated hepatic steatosis. This could be explained by improved glucose metabolism, fat catabolism, bile acid metabolism, and lipid storage and transport. We identified PPARs as important regulators and observed differences in effects on insulin resistance, inflammation and oxidative stress between Stevia-derived compounds. We conclude that Stevia-derived compounds reduce hepatic steatosis to a similar extent, despite differences in effects on glucose and lipid metabolism, and inflammation and oxidative stress. Thus our data show that liver toxicity can be reduced through several pathophysiological changes. Further identification of active metabolites and underlying mechanisms are warranted.

Keywords: Insulin resistance; Liver steatosis; Liver toxicity; Metabolomics; Obesity; Steviosides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism
  • Animals
  • Bile Acids and Salts / metabolism
  • Disease Models, Animal
  • Diterpenes, Kaurane / pharmacology
  • Fatty Liver / drug therapy*
  • Glucose / metabolism
  • Glucosides / pharmacology
  • Glutathione / metabolism
  • Insulin Resistance
  • Lipid Metabolism / drug effects
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Metabolomics
  • Mice
  • Mice, Obese
  • Obesity / drug therapy
  • Oxidative Stress / drug effects
  • Peroxisome Proliferator-Activated Receptors / metabolism
  • Plant Preparations / pharmacology*
  • Stevia / chemistry*
  • Transcriptome*


  • Amino Acids
  • Bile Acids and Salts
  • Diterpenes, Kaurane
  • Glucosides
  • Peroxisome Proliferator-Activated Receptors
  • Plant Preparations
  • stevioside
  • steviol
  • rebaudioside A
  • Glutathione
  • Glucose