SIRT1 and other sirtuins in metabolism

Chang, Hung-Chun; Guarente, Leonard

doi:10.1016/j.tem.2013.12.001

Cited by 913 publications

(720 citation statements)

References 120 publications

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“…Sirt1 deacetylates histones H3K9, H3K56, H4K16, and H1K26 as well as many nonhistone targets thereby contributing to the maintenance of metabolic homeostasis and genomic integrity (3,4). Sirt1 was also identified as a critical component of lifespan extension in response to calorie restriction in several model organisms, although its exact contribution is still under debate (5).…”

mentioning

confidence: 99%

Sirt7 promotes adipogenesis in the mouse by inhibiting autocatalytic activation of Sirt1

Fang

Ianni

Smolka

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Sirtuins (Sirt1-Sirt7) are NAD + -dependent protein deacetylases/ ADP ribosyltransferases, which play decisive roles in chromatin silencing, cell cycle regulation, cellular differentiation, and metabolism. Different sirtuins control similar cellular processes, suggesting a coordinated mode of action but information about potential cross-regulatory interactions within the sirtuin family is still limited. Here, we demonstrate that Sirt1 requires autodeacetylation to efficiently deacetylate targets such as p53, H3K9, and H4K16. Sirt7 restricts Sirt1 activity by preventing Sirt1 autodeacetylation causing enhanced Sirt1 activity in Sirt7 −/− mice. Increased Sirt1 activity in Sirt7 −/− mice blocks PPARγ and adipocyte differentiation, thereby diminishing accumulation of white fat. Thus, reduction of Sirt1 activity restores adipogenesis in Sirt7 −/− adipocytes in vitro and in vivo. We disclosed a principle controlling Sirt1 activity and uncovered an unexpected complexity in the crosstalk between two different sirtuins. We propose that antagonistic interactions between Sirt1 and Sirt7 are pivotal in controlling the signaling network required for maintenance of adipose tissue.sirtuin | acetylation | adipogenesis T he seven sirtuins in mammals (Sirt1-Sirt7) are involved in the regulation of essential cellular processes. Sirtuins rapidly adjust the activity of chromatin, transcription factors, metabolic enzymes, and structural proteins to cellular needs by deacetylating a broad range of targets. The ability to sense metabolic alterations and various stressors enable sirtuins to adapt cellular homeostasis to varying conditions. It seems likely that this feature of sirtuins is crucial to prevent age-dependent pathologies and promote a healthy lifespan (1, 2).Sirt1 is the most widely studied mammalian sirtuin showing the highest homology to the founding member of the sirtuin family, the yeast silence information regulator, Sir2. Sirt1 deacetylates histones H3K9, H3K56, H4K16, and H1K26 as well as many nonhistone targets thereby contributing to the maintenance of metabolic homeostasis and genomic integrity (3, 4). Sirt1 was also identified as a critical component of lifespan extension in response to calorie restriction in several model organisms, although its exact contribution is still under debate (5). The functions of Sirt7 have attracted less attention compared with Sirt1.

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confidence: 99%

Sirt7 promotes adipogenesis in the mouse by inhibiting autocatalytic activation of Sirt1

Fang

Ianni

Smolka

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…The NAD-dependent protein deacetylase, Sirt-1, is also recognized as another regulator of energy metabolism [37,[40][41][42]. Sirt-1 has critically-important roles in regulating cellular metabolism and controlling responses to cellular stresses via the regulation of target proteins, and is closely involved in the pathophysiology of stressinduced degenerative diseases including OA [9,13,20,21].…”

Section: Discussionmentioning

confidence: 99%

The Nicotinamide Adenine Dinucleotide (NAD)-Dependent Deacetylase Sirtuin-1 Regulates Chondrocyte Energy Metabolism through the Modulation of Adenosine Monophosphate-Activated Protein Kinase (AMPK) in Osteoarthritis(OA)

Kobayashi¹,

Terauchi²,

Yui³

et al. 2017

J Arthritis

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To clarify how the osteoarthritis (OA)-induced catabolic factor interleukin (IL)-1β affects chondrocyte energy metabolism, and especially to define the downstream pathway linking nicotinamide adenine dinucleotide (NAD)-dependent deacetylase Sirtuin-1 (Sirt-1) to energy metabolism in OA chondrocytes. Human chondrocytes were isolated from articular cartilage samples of patients with OA. The level of energy metabolism of OA chondrocytes was evaluated by monitoring the activity of the energy metabolic sensor, adenosine monophosphate-activated protein kinase (AMPK) and the level of production of adenosine triphosphate (ATP) in chondrocytes in the presence or absence of t IL-1β (10 ng/mL). Effects of IL-1β on anabolic and catabolic activities of chondrocytes were analyzed by the levels of production of proteoglycan and matrix metalloproteinase (MMP)-13, respectively. Experiments involving pre-treatment with Sirt-1 inhibitor were also performed to investigate the underlying regulatory mechanism linking Sirt-1 to chondrocyte energy metabolism. IL-1β significantly inhibited the activity of AMPK and production of ATP in OA chondrocytes. The energy metabolism disruption mediated by IL-1β was further decreased by pretreatment with Sirt-1 inhibitor in OA chondrocytes. Treatment with IL-1β significantly decreased the level of proteoglycan production and significantly increased the level of MMP-13 secretion by chondrocytes. These chondrocyte activities were also reduced by pre-treatment with the Sirt-1 inhibitor in OA chondrocytes. IL-1β inhibits the AMPK -ATP energy metabolic pathway in OA chondrocytes. Our findings also suggest that Sirt-1 activity is involved in anabolic and catabolic cellular activities and that Sirt-1 modulates ATP production through functional regulation of the energy sensor AMPK in chondrocytes.

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“…Classical HDACs are further divided into four families (classes I, IIa, IIb and IV) based on their homology to yeast proteins. Like HATs, HDACs do not act individually but instead act as a part of large multiprotein complexes that participate in transcriptional regulation pathways (Haberland et al 2009;Chang & Guarente 2014).…”

Section: Post-translational Histone Modificationsmentioning

confidence: 99%

Epigenetics: from the past to the present

Villota-Salazar

Mendoza‐Mendoza

González-Prieto

2016

Frontiers in Life Science

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The definition of epigenetics is still under intense debate; however, its concept has evolved since it was originally introduced in 1939 by Conrad Hal Waddington as a way to reconcile antagonistic views between the school of preformationism and the school of epigenesis. The characterization of a large number of phenomena that diverge from the dogmas of classical genetics, and the discovery of the molecular mechanisms through which these phenomena occur, has given rise to a new area of study with important implications for biological sciences. Interactions between the environment and the DNA through modifications on the chromatin are not only responsible for the expression of a normal phenotype, these may be involved in the development of various pathologies. The epigenome, as the bridge between the genome and the phenotype, is no doubt one of the most interesting current ideas in genetics and is so revolutionary that it may change our present notions about inheritance and evolution. In this review, we made a compilation of the most important events in the history of epigenetics, its implications and some perspectives to the future.

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SIRT1 and other sirtuins in metabolism

Cited by 913 publications

References 120 publications

Sirt7 promotes adipogenesis in the mouse by inhibiting autocatalytic activation of Sirt1

Sirt7 promotes adipogenesis in the mouse by inhibiting autocatalytic activation of Sirt1

The Nicotinamide Adenine Dinucleotide (NAD)-Dependent Deacetylase Sirtuin-1 Regulates Chondrocyte Energy Metabolism through the Modulation of Adenosine Monophosphate-Activated Protein Kinase (AMPK) in Osteoarthritis(OA)

Epigenetics: from the past to the present

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