Disparate Metabolic Response to Fructose Feeding Between Different Mouse Strains

Sci Rep. 2015 Dec 22;5:18474. doi: 10.1038/srep18474.


Diets enriched in fructose (FR) increase lipogenesis in the liver, leading to hepatic lipid accumulation and the development of insulin resistance. Previously, we have shown that in contrast to other mouse strains, BALB/c mice are resistant to high fat diet-induced metabolic deterioration, potentially due to a lack of ectopic lipid accumulation in the liver. In this study we have compared the metabolic response of BALB/c and C57BL/6 (BL6) mice to a fructose-enriched diet. Both strains of mice increased adiposity in response to FR-feeding, while only BL6 mice displayed elevated hepatic triglyceride (TAG) accumulation and glucose intolerance. The lack of hepatic TAG accumulation in BALB/c mice appeared to be linked to an altered balance between lipogenic and lipolytic pathways, while the protection from fructose-induced glucose intolerance in this strain was likely related to low levels of ER stress, a slight elevation in insulin levels and an altered profile of diacylglycerol species in the liver. Collectively these findings highlight the multifactorial nature of metabolic defects that develop in response to changes in the intake of specific nutrients and the divergent response of different mouse strains to dietary challenges.

MeSH terms

  • Adiposity / drug effects
  • Animals
  • Biomarkers / metabolism
  • Body Weight / drug effects
  • Cells, Cultured
  • Endoplasmic Reticulum Stress / drug effects
  • Energy Metabolism / drug effects
  • Enzyme Activation / drug effects
  • Fatty Acids / metabolism
  • Feeding Behavior / drug effects*
  • Fructose / pharmacology*
  • Glucose / metabolism
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Insulin / metabolism
  • Lipid Metabolism / drug effects
  • Lipogenesis / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Metabolism / drug effects*
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Muscles / drug effects
  • Muscles / metabolism
  • Oxidation-Reduction
  • Phosphorylation / drug effects
  • Protein Kinase C / metabolism
  • Protein Transport / drug effects
  • Signal Transduction / drug effects


  • Biomarkers
  • Fatty Acids
  • Insulin
  • Fructose
  • Protein Kinase C
  • Glucose