Plasticity of lifelong calorie-restricted C57BL/6J mice in adapting to a medium-fat diet intervention at old age

Fenni Rusli, Mark V. Boekschoten, Vincenzo Borelli, Chen Sun, Carolien Lute, Aswin L Menke, Joost van den Heuvel, Stefano Salvioli, Claudio Franceschi, Michael Muller, Wilma T Steegenga

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Abstract

Calorie restriction (CR) is a dietary regimen that supports healthy aging. In this study we investigated the systemic and liver-specific responses caused by a diet switch to a medium-fat (MF) diet in 24-month-old life-long, CR-exposed mice. This study aimed to increase the knowledge base on dietary alterations of gerontological relevance. Nine-week-old C57BL/6J mice were exposed either to a control, CR or MF diet. At the age of 24 months, a subset of mice of the CR group was transferred to ad libitum MF feeding (CR-MF). The mice were sacrificed at the age of 28 months, then biochemical and molecular analyses were performed. Our results showed that, despite the long-term exposure to the CR regimen, mice in the CR-MF group displayed hyperphagia, rapid weight gain, and hepatic steatosis. However, no hepatic fibrosis/injury or alteration in CR-improved survival was observed in the diet switch group. The liver transcriptomic profile of CR-MF mice largely shifted to a profile similar to the MF-fed animals but leaving ~22% of the 1578 differentially regulated genes
between the CR and MF diet groups comparable with the expression of the life-long CR group. Therefore, although the diet switch was performed at an old age, the CR-MF-exposed mice showed plasticity in coping with the challenge of a MF diet without developing severe liver pathologies.
Original languageEnglish
Article numbere12696
JournalAging Cell
Volume17
Issue number2
Early online date21 Dec 2017
DOIs
Publication statusPublished - Apr 2018

Keywords

  • aging
  • long-term CR
  • liver
  • NAFLD
  • transcriptomics
  • glycomics

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