C57BL/6J substrain differences in response to high-fat diet intervention

Majken Storm Siersbæk, Nicholas Ditzel, Eva Kildall Hejbøl, Stine Marie Præstholm, Lasse Kruse Markussen, Fabio Avolio, Lingzi Li, Lasse Lehtonen, Axel Kornerup Hansen, Henrik Daa Schrøder, Lukasz Krych, Susanne Mandrup, Louise Langhorn, Peter Bollen, Lars Grøntved

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Abstract

C57BL/6J-related mouse strains are widely used animal models for diet-induced obesity (DIO). Multiple vendors breed C57BL/6J-related substrains which may introduce genetic drift and environmental confounders such as microbiome differences. To address potential vendor/substrain specific effects, we compared DIO of C57BL/6J-related substrains from three different vendors: C57BL/6J (Charles Rivers), C57BL/6JBomTac (Taconic Bioscience) and C57BL/6JRj (Janvier). After local acclimatization, DIO was induced by either a high-fat diet (HFD, 60% energy from fat) or western diet (WD, 42% energy from fat supplemented with fructose in the drinking water). All three groups on HFD gained a similar amount of total body weight, yet the relative amount of fat percentage and mass of inguinal- and epididymal white adipose tissue (iWAT and eWAT) was lower in C57BL/6JBomTac compared to the two other C57BL/6J-releated substrains. In contrast to HFD, the three groups on WD responded differently in terms of body weight gain, where C57BL/6J was particularly prone to WD. This was associated with a relative higher amount of eWAT, iWAT, and liver triglycerides. Although the HFD and WD had significant impact on the microbiota, we did not observe any major differences between the three groups of mice. Together, these data demonstrate significant differences in HFD- and WD-induced adiposity in C57BL/6J-related substrains, which should be considered in the design of animal DIO studies.

Original languageEnglish
Article number14052
JournalScientific Reports
Volume10
Issue number1
Number of pages15
ISSN2045-2322
DOIs
Publication statusPublished - 2020

Keywords

  • Absorptiometry, Photon
  • Animals
  • Body Weight
  • Diet, High-Fat
  • Glucose/administration & dosage
  • Insulin/blood
  • Liver/metabolism
  • Mice
  • Mice, Inbred C57BL
  • Obesity/genetics
  • Organ Size
  • Species Specificity
  • Triglycerides/metabolism
  • Weight Gain

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