Boutant 2016 Cell Rep
|Boutant M, Kulkarni SS, Joffraud M, Raymond F, Métairon S, Descombes P, Cantó C (2016) SIRT1 gain of function does not mimic or enhance the adaptations to intermittent fasting. Cell Rep 14:2068-75.|
Abstract: Caloric restriction (CR) has been shown to prevent the onset of insulin resistance and to delay age-related physiological decline in mammalian organisms. SIRT1, a NAD(+)-dependent deacetylase enzyme, has been suggested to mediate the adaptive responses to CR, leading to the speculation that SIRT1 activation could be therapeutically used as a CR-mimetic strategy. Here, we used a mouse model of moderate SIRT1 overexpression to test whether SIRT1 gain of function could mimic or boost the metabolic benefits induced by every-other-day feeding (EODF). Our results indicate that SIRT1 transgenesis does not affect the ability of EODF to decrease adiposity and improve insulin sensitivity. Transcriptomic analyses revealed that SIRT1 transgenesis and EODF promote very distinct adaptations in individual tissues, some of which can even be metabolically opposite, as in brown adipose tissue. Therefore, whereas SIRT1 overexpression and CR both improve glucose metabolism and insulin sensitivity, the etiologies of these benefits are largely different.
Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
• Keywords: SIRT1, Caloric restriction, Mitochondria
• O2k-Network Lab: CH Lausanne Canto C
Labels: MiParea: Respiration, Genetic knockout;overexpression, Exercise physiology;nutrition;life style
Organism: Mouse Tissue;cell: Skeletal muscle, Liver, Fat Preparation: Permeabilized tissue, Homogenate
Coupling state: OXPHOS, ET Pathway: N, NS HRR: Oxygraph-2k