Intermittent calorie restriction largely counteracts the adverse health effects of a moderate-fat diet in aging C57BL/6J mice

Fenni Rusli, Carolien Lute, Mark V Boekschoten, Miriam van Dijk, Klaske van Norren, Aswin L Menke, Michael Müller, Wilma T Steegenga

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Scope: Calorie restriction (CR) has been shown to extend life- and health-span in model species. For most humans, a life-long CR diet is too arduous to adhere to. The aim of this study was to explore whether weekly intermittent CR can 1) provide long-term beneficial effects and 2) counteract diet-induced obesity in male aging mice.

Methods and results: In this study we have exposed C57Bl/6J mice for 24 months to an intermittent (INT) diet, alternating weekly between CR of a control diet and ad libitum moderate-fat (MF) feeding. This weekly intermittent CR significantly counteracted the adverse effects of the MF diet on mortality, body weight and liver health markers in male 24-month-old mice. Hepatic gene expression profiles of INT-exposed animals appeared much more comparable to CR than to MF-exposed mice. At 12 months of age, a subgroup of MF-exposed mice was transferred to the INT diet. Gene expression profiles in the liver of the 24-month-old diet switch mice were highly similar to the INT-exposed mice. However, a small subset of genes was consistently changed by the MF diet during the first phase of life.

Conclusion: Weekly intermittent CR largely, but not completely, reversed adverse effects caused by a MF diet.
Original languageEnglish
Article number1600677
JournalMolecular Nutrition & Food Research
Issue number5
Early online date21 Mar 2017
Publication statusPublished - May 2017


  • Aging
  • Intermittent calorie restriction
  • Liver
  • Moderate-fat diet
  • Obesity
  • Transcriptomics

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