title: SIRT1 Gain of Function Does Not Mimic or Enhance the Adaptations to Intermittent Fasting.
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 be 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.
authors.affiliation: Nestlé Institute of Health Sciences (NIHS), 1015 Lausanne, Switzerland.
authors.forename: Marie
authors.initials: M
authors.lastname: Boutant
authors.affiliation: Nestlé Institute of Health Sciences (NIHS), 1015 Lausanne, Switzerland.
authors.forename: Sameer S
authors.initials: SS
authors.lastname: Kulkarni
authors.affiliation: Nestlé Institute of Health Sciences (NIHS), 1015 Lausanne, Switzerland.
authors.forename: Magali
authors.initials: M
authors.lastname: Joffraud
authors.affiliation: Nestlé Institute of Health Sciences (NIHS), 1015 Lausanne, Switzerland.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Raymond
authors.affiliation: Nestlé Institute of Health Sciences (NIHS), 1015 Lausanne, Switzerland.
authors.forename: Sylviane
authors.initials: S
authors.lastname: Métairon
authors.affiliation: Nestlé Institute of Health Sciences (NIHS), 1015 Lausanne, Switzerland; École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Descombes
authors.affiliation: Nestlé Institute of Health Sciences (NIHS), 1015 Lausanne, Switzerland; École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland. Electronic address: carlos.cantoalvarez@rd.nestle.com.
authors.forename: Carles
authors.initials: C
authors.lastname: Cantó
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D005215:Fasting / Q000502:physiology*; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D008297:Male; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism; D010805:Physical Conditioning, Animal; D056564:Sirtuin 1 / Q000502:physiology*; D059467:Transcriptome
chemical_list: C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D005947:Glucose
keywords: SIRT1; caloric restriction; mitochondria