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Sirtuin 1 (SirT1), the mammalian homolog of yeast silent information-regulator 2 (Sir2), is an NAD+-dependent histone deacetylase and an important coordinator of the mammalian metabolic response to fasting and caloric restriction (10¨C12). During periods of nutrient deprivation, elevated levels of SirT1 in the liver increase hepatic glucose production (10) and induce the expression of oxidative machinery (13). Accordingly, experimental knockdown of SirT1 reduces fasting plasma glucose levels and increases whole-body insulin sensitivity by reducing hepatic glucose production (11,14). In adipose tissue, SirT1 enhances metabolic efficiency by promoting adiponectin production (15). Conversely, adipocyte SirT1 expression is suppressed by high-fat feeding in rodents (16), and its levels are also markedly reduced in the adipose tissue of obese humans and genetically obese rodents (16,17).

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