Open AccessPlasticity of lifelong calorie‐restricted C57 BL /6J mice in adapting to a medium‐fat diet intervention at old age
Author(s) -
Rusli Fenni,
Boekschoten Mark V.,
Borelli Vincenzo,
Sun Chen,
Lute Carolien,
Menke Aswin L.,
Heuvel Joost,
Salvioli Stefano,
Franceschi Claudio,
Müller Michael,
Steegenga Wilma T.
Publication year - 2018
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12696
Subject(s) - biology , calorie restriction , fatty liver , steatosis , regimen , medicine , endocrinology , calorie , physiology , disease
Summary 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 lifelong, CR ‐exposed mice. This study aimed to increase the knowledge base on dietary alterations of gerontological relevance. Nine‐week‐old C57 BL /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, and 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 1,578 differentially regulated genes between the CR and MF diet groups comparable with the expression of the lifelong 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.