Sirtuins may mediate temperature-induced metabolic remodeling in threespine stickleback

The molecular pathway governing metabolic remodeling in response to
temperature in fishes is unknown. We tested the hypothesis that sirtuins,
a family of NAD+ dependent lysine deacetylases, drives an increase in
aerobic metabolism in response to cold acclimation in stickleback.
Stickleback were acclimated to 5, 12 and 20°C and sirtuin activity
measured in liver, oxidative and glycolytic muscles using a Promega
SIRT-Glo Assay kit. Protein levels of SIRT1 and SIRT3 were quantified
using custom antibodies and capillary western blotting. In a second set of
experiments, sirtuin activity was inhibited by feeding with EX-527 or
activated by feeding with the NAD+ pre-cursor, nicotinamide mononucleotide
(NMN). Standard metabolic rate (SMR) was measured using intermittent flow
respirometry. Mitochondrial respiration rates were measured in
permeabilized liver tissue using a substrate-uncoupler-inhibitor titration
protocol . Sirtuin activity significantly increased in response to cold
acclimation in liver and oxidative and glycolytic muscles but SIRT3
protein levels declined and SIRT1 protein was undetectable, suggesting one
or more other SIRT isoforms contribute to an increase in sirtuin activity
in response to cold acclimation. Inhibiting sirtuin activity with EX-527
decreased SMR and the activity of complex I in liver, providing further
support for the role of sirtuins in metabolic remodeling in
stickleback.