Table 2.

Sirtuin metabolic functions.

Gene	Functions	Ref.
SIRT1	Pancreatic β cells
	▪ Increases insulin gene transcription	[75–79]
	▪ Decreases UCP2 gene transcription	[75,76,78,207]
	▪ Increases glucose-stimulated insulin secretion	[75–79]
	▪ Protects against cytokine toxicity via NF-κβ downregulation	[79]
	▪ Protects against oxidative stress via upregulation of NeuroD and MafA	[175]
	Liver
	▪ Regulates gluconeogenesis	[32,80,82–88]
	▪ Inhibits glycolysis	[84,89,90]
	▪ Inhibits lipogenesis	[91,95,96]
	▪ Increases fatty acid oxidation	[92]
	▪ Inhibits cholesterol biosynthesis	[96–98]
	▪ Improves hepatic insulin sensitivity	[82]
	▪ Inhibits oxidative stress, inflammation and ER stress	[82,92,94,208]
	▪ Regulates circadian rhythms	[22,23]
	▪ Modulates NAD biosynthesis	[20,21]
	Brain
	▪ Mediobasal hypothalamic SIRT1 inhibits hepatic glucose production	[117]
	▪ Central SIRT1 positively regulates food intake and energy expenditure	[118–124]
	▪ Regulates physical activities	[123]
	Skeletal muscle
	▪ Increases insulin sensitivity	[99,103]
	▪ Increases mitochondrial biogenesis	[100–102]
	▪ Increases fatty acid oxidation	[100,104]
	Adipose tissue
	▪ Increases adiponectin biosynthesis and secretion	[109–111]
	▪ Increases lipolysis	[112,113]
	▪ Inhibits adipogenesis	[112]
SIRT2	Liver
	▪ Increases hepatic gluconeogenesis via deacetylation of PEPCK	[32]
	Adipose tissue
	▪ Decreases oxidative stress via deacetylation of FOXO3	[116]
	▪ Inhibits adipocyte differentiation via deacetylation of FOXO1	[35,115]
SIRT3	Liver
	▪ Regulates energy homeostasis via control of ETC complexes I and II	[54]
	▪ Reduces oxidative stress via deacetylation of SOD2	[51]
	▪ Increases fatty acid oxidation via deacetylation of LCAD and others	[39,43,50,53
	▪ Increases ketone body production via deacetylation of HMGCS2	[50]
	▪ Promotes the urea cycle via deacetylation of OTC	[43]
	Skeletal muscle
	▪ Induced by fasting, caloric restriction and exercise	[105–107]
	▪ Decreased by high-fat diet	[40,41,107]
	▪ Inhibits mitochondrial protein synthesis via deacetylation of MRPL10	[47]
	▪ Increases mitochondrial oxidation	[39,40]
	▪ Decreases ROS and insulin resistance	[40,108]
	▪ Increases mitochondrial biogenesis	[108]
	Brain
	▪ Protects against age-related hearing loss by reducing oxidative damage	[48]
SIRT4	Pancreatic β cells
	▪ Decreases insulin secretion via inhibition of GDH	[8,9]
SIRT5	Liver
	▪ Regulates the urea cycle via deacetylation of CPS1	[58,59]
SIRT6	Liver
	▪ Inhibits glycolysis and lipogenesis via deacetylation of H3K9	[64]
	▪ Increases fatty acid oxidation via deacetylation of H3K9	[64]
	Brain
	▪ Regulates somatic growth and adiposity via deacetylation of H3K9 and H3K56 in the brain	[63]
	Skeletal muscle
	▪ Inhibits basal- and insulin-stimulated glucose uptake	[61,62]
	Adipose tissue
	▪ Decreases triglyceride synthesis via downregulation of DGAT1	[65]
	▪ Inhibits glucose uptake	[61]
SIRT7	Regulates Pol I transcription and p53 function, particularly protects against stress, apoptosis and inflammation in the heart	[72,74]

ETC: Electron transport chain; GDH: Glutamate dehydrogenase; ROS: Reactive oxygen species.