Table 1.

Prominent energy metabolism phenotypes observed in SIRT1 gain-of-function models through genetic mechanisms.

Targeted tissue	Genetic strategy	Prominent phenotypes observed	References
Whole body	Overexpression (moderate)	Protection against dietary and age-related metabolic damage.	Pfluger et al. [4]
			Banks et al. [5]
		Similar lifespan as WT mice	Herranz et al. [3]
	Overexpression (moderate)	Calorie-restriction like behavior	Bordone et al. [8]
	Overexpression (moderate)	Higher susceptibility to atherosclerotic lesions when fed a atherogenic diet	Quiang et al. [60]
	Overexpression (high)	Higher muscle mitochondrial content	Price et al. [9]
Liver	Overexpression (adenoviral delivery)	Positive regulation of hepatic glucose production and inhibition of lipid anabolism	Rodgers et al. [21]
	Overexpression (adenoviral delivery)	Attenuation of hepatic glucose production and insulin resistance in ob/ob mice	Wang et al. [20]
Muscle	Overexpression	Similar aspect, insulin sensitivity and adaptation to calorie restriction as in wild-type mice	White et al. [40]
	MCK-Cre
Adipose tissue	Overexpression	Prevention against age-induced deterioration of insulin sensitivity and ectopic lipid distribution. Reduction of whole body fat mass and enhanced locomotor activity	Xu et al. [64]
	Ap2-Cre
Pancreas	Overexpression	Enhanced glucose-induced insulin secretion	Moynihan et al. [75]
	SIRT1 insertion under the human insulin promoter
Brain	Whole brain overexpression	Enhanced foraging behavior upon calorie restriction	Satoh et al. [86,90]
	SIRT1 insertion under the mouse PrP promoter	Lifespan extension