rs1000b@yahoo.com
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 Posted: Fri Oct 10, 2008 2:39 am Post subject: SirT1 gain of function increases energy efficiency and preve |
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Cell Metab. 2008 Oct;8(4):333-41.
SirT1 gain of function increases energy efficiency and prevents
diabetes in mice.
Banks AS, Kon N, Knight C, Matsumoto M, Gutiérrez-Juárez R, Rossetti
L, Gu W, Accili D.
Naomi Berrie Diabetes Center, Department of Medicine, College of
Physicians and Surgeons of Columbia University, New York, NY 10032,
USA.
In yeast, worms, and flies, an extra copy of the gene encoding the
Sirtuin Sir2 increases metabolic efficiency, as does administration of
polyphenols like resveratrol, thought to act through Sirtuins. But
evidence that Sirtuin gain of function results in increased metabolic
efficiency in mammals is limited. We generated transgenic mice with
moderate overexpression of SirT1, designed to mimic the Sirtuin gain
of function that improves metabolism in C. elegans. These mice exhibit
normal insulin sensitivity but decreased food intake and locomotor
activity, resulting in decreased energy expenditure. However, in
various models of insulin resistance and diabetes, SirT1 transgenics
display improved glucose tolerance due to decreased hepatic glucose
production and increased adiponectin levels, without changes in body
weight or composition. We conclude that SirT1 gain of function primes
the organism for metabolic adaptation to insulin resistance,
increasing hepatic insulin sensitivity and decreasing whole-body
energy requirements. These findings have important implications for
Sirtuin-based therapies in humans.
PMID: 18840364 [PubMed - in process] |
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