The liver is a critical hub for a variety of metabolic and physiological processes. In the liver, sirtuins (SIRTs) regulate metabolism and play important physiological functions including hepatic glucose and fatty acid metabolism, mitochondrial function, hepatic gluconeogenesis, insulin secretion, and the maturation of fat cells. Accordingly, differential regulation of SIRTs is associated with a variety of liver defects. Especially, downregulation of SIRT1 has been directly connected to liver inflammation, fatty liver diseases, hepatic stellate cells activation, and fibrosis progression. Activation of SIRTs 1, 2, and 6 plays a crucial role in the replication and transcription of hepatitis B virus. Clinical studies showed that the activation of SIRTs 1, 3, 5, and 6 is necessary for antilipidemic effects, while downregulation of SIRTs 1 and 3 caused lipogenesis. SIRTs 1, 5, and 7 upregulation has been reported in patients with hepatocellular carcinoma (HCC), whereas the expression of SIRT2 and 3 was downregulated during HCC progression. The role of SIRT6 in HCC is ambiguous whether tumor suppressor or oncogenic. Therefore SIRT1 activators are proposed to be used for the treatment of liver inflammation, fatty diseases, and hepatic fibrosis. Selective SIRTs 1, 5, 6, and 7 inhibitors and activators of SIRTs 2 and 3 are developed for their potential antitumor actions.
Elsevier, Sirtuin Biology in Medicine, Targeting New Avenues of Care in Development, Aging, and Disease, 2021, Pages 329-340
