Diverse Roles of SIRT1 in Cancer Biology and Lipid Metabolism

Abstract

SIRT1, an NAD+-dependent deacetylase, has been described in the literature as a major player in the regulation of cellular stress responses. Its expression has been shown to be altered in cancer cells, and it targets both histone and non-histone proteins for deacetylation and thereby alters metabolic programs in response to diverse physiological stress. Interestingly, many of the metabolic pathways that are influenced by SIRT1 are also altered in tumor development. Not only does SIRT1 have the potential to regulate oncogenic factors, it also orchestrates many aspects of metabolism and lipid regulation and recent reports are beginning to connect these areas. SIRT1 influences pathways that provide an alternative means of deriving energy (such as fatty acid oxidation and gluconeogenesis) when a cell encounters nutritive stress, and can therefore lead to altered lipid metabolism in various pathophysiological contexts. This review helps to show the various connections between SIRT1 and major pathways in cellular metabolism and the consequence of SIRT1 deregulation on carcinogenesis and lipid metabolism.

Sirt1 is involved in decreased bone formation in aged apolipoprotein E-deficient mice

“…To further analyze the mechanisms mediating this rapid decrease in bone mass and bone formation in aged apoE -/mice, we first measured Sirt1 expression in bone tissues in young and aged apoE -/mice. Sirt1 is the founding member of a group of proteins that have been well studied in aging research [39,40] , and Sirt1 affects a variety of biological functions, including DNA repair, energy metabolism, tumor suppression, and mitochondrial homeostasis [41,42] . In addition, transgenic mice with approximately 2-fold higher levels of global Sirt1 expression are protected against metabolic decline due to aging [43] .…”

SirT1 activator represses the transcription of TNF-α in THP-1 cells of a sepsis model via deacetylation of H4K16

“…It is not surprising that SirT1 has a number of roles in multiple tissues through its effects on diverse physiological processes (10,11). Previous studies have further revealed the role of SirT1 in sepsis.…”

Systems approach to characterize the metabolism of liver cancer stem cells expressing CD133

“…4a). SIRT1 induces fatty acid oxidation by deacetylating its target genes in cancer4142. In particular, PPARγ co-activator-1α (PGC-1α) is the potent target of SIRT1 and induces the transcription of target genes responsible for fatty acid oxidation by forming a complex with PPARγ and RXRα4344.…”