Food anticipatory activity on a calorie-restricted diet is independent of Sirt1

Abstract

A number of studies have demonstrated that the Sirtuin family member, Sirt1, is a key integrator of growth, metabolism, and lifespan. Sirt1 directly interacts with and deacetylates key regulators of the circadian clock, positioning it to be an important link between feeding and circadian rhythms. In fact, one study suggests that Sirt1 is necessary for behavioral anticipation of limited daily food availability, a circadian process termed food anticipatory activity (FAA). In their study, mice overexpressing Sirt1 had enhanced FAA, while mice lacking Sirt1 had little to no FAA. Based on the supposition that Sirt1 was indeed required for FAA, we sought to use Sirt1 deletion to map the neural circuitry responsible for FAA. We began by inactivating Sirt1 using the cell-type specific Cre-driver lines proopiomelanocortin, but after observing no effect on body weight loss or FAA we then moved on to more broadly neuronal Cre drivers Ca2+/calmodulin-dependent protein kinase II and nestin. As neither of these neuronal deletions of Sirt1 had impaired FAA, we then tested 1) a broad postnatal tamoxifen-inducible deletion, 2) a complete, developmental knockout of Sirt1, and 3) a gene replacement, catalytically inactive, form of Sirt1; but all of these mice had FAA similar to controls. Therefore, our findings suggest that FAA is completely independent of Sirt1.

The Mysterious Food-Entrainable Oscillator: Insights from Mutant and Engineered Mouse Models

“…2B). However, a new study showed that FAA was normal during restricted feeding with caloric restriction in global Sirt1 −/− mice and also in several cell-type specific Sirt1 mutant mice (Table 5) (Assali et al, 2018). Further studies are necessary to address the inconsistent findings in Sirt1 −/− mice.…”

Addition of an N-Terminal Poly-Glutamate Fusion Tag Improves Solubility and Production of Recombinant TAT-Cre Recombinase in Escherichia coli

“…When lethality is caused by a tissue-specific gene knockout after Cre-loxP recombination in genetically modified floxed mice, TAT-Cre can be employed for subsequent investigation of the mechanism. To prevent the above lethality, a tamoxifen-inducible Cre system has been devised [ 33 , 34 ]. Another purpose of the inducible system is prevention of the chronic effects of gene deletion during the embryonic period.…”