SIRT5 Regulates Brown Adipocyte Differentiation and Browning of Subcutaneous White Adipose Tissue

Shuai, Lei; Zhang, Lina; Li, Bohan; Tang, Chunlan; Wu, Lingyan; Li, Jia

doi:10.2337/db18-1103

Cited by 41 publications

(47 citation statements)

References 49 publications

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“…sirt5 was found to be essential for activation of brown adipogenic genes, and adipocyte differentiation in vitro and its knockout leads to the decrease in intracellular α-ketoglutarate concentration, which results in elevated histone methylation and transcriptional repression of pparγ and Prdm16. Therefore sirt5 KO mice present diminished browning capacity of WAT with subsequent cold intolerance [30].…”

Section: Sirts and Adipocyte Browningmentioning

confidence: 96%

Role of Sirtuins in Adipose Tissue Development and Metabolism

Kuryłowicz¹

2019

Adipose Tissue - An Update

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Sirtuins (silent information regulators, sirts) via modification of histones, as well as transcription factors and co-regulators, control expression of other genes, particularly those involved in the organism response to stress. Detection of sirtuin expression in adipocytes initiated interest in their role in adipose tissue development and metabolism. This chapter presents how sirtuins control the critical steps of preadipocytes' differentiation and proliferation, as well as the process of adipose tissue browning. Moreover, it shows in vitro and in vivo data proving that sirtuins are involved in the regulation of lipogenesis, lipolysis, and secretory activity of adipose tissue. Due to all these reasons, sirtuins may constitute potential targets in the treatment of obesity and related complications. 1 2. A short review of the sirt system The sirts are highly conserved regulatory proteins present almost in all species. Initially, they have been identified as class III histone deacetylases, nicotinamide adenine dinucleotide (NAD)-dependent enzymes responsible for the removal of acetyl groups from lysine residues in proteins, while some members of this family act also as mono-ADP-ribosyltransferases. Since acetylation and deacetylation are essential mechanisms of posttranslational modifications of proteins determining their activity, sirts were found to be involved in the regulation of distinct cellular pathways including, among others, those related to cell survival, apoptosis, inflammatory and stress responses, as well as lipid and glucose homeostases [2].In human, seven sirt genes (sirts) have been identified that encode seven sirt enzymes of different structure, cellular localization, and tissue expression. All of them share a common conserved catalytic core region consisting of approximately 275 amino acids, forming a Rossmann fold domain (characteristic of NAD + /NADH-binding proteins) and a zinc-binding domain connected by several loops [2]. Outside the catalytic core, sirt enzymes possess variable N-and C-terminal regions that decide about their enzymatic activities, binding partners and substrates, as well as subcellular localization [3]. sirt1, sirt6, and sirt7 localize predominantly in the nucleus where via modifications of transcription factors, cofactors, and histones they participate in the regulation of energy metabolism, stress and inflammatory responses, DNA repair (sirt1 and sirt6), and rDNA transcription (sirt7) [4]. sirt2 is a cytoplasmic sirtuin and plays a role in cell cycle control [5]. sirt3 can be found in mitochondria where it takes part in the regulation of enzymes involved, e.g., in glycolysis, fatty acid (FA) oxidation, ketone body synthesis, and the catabolism of amino acids as well as of apoptosis and oxidative stress pathways. This sirtuin also has as a nuclear full-length form (FL-sirt3) that is processed to the short mitochondrial form. Therefore, sirt3 may regulate cellular metabolism both at the transcriptional and posttranscriptional levels. sirt4 is also localized in mitochondria...

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Section: Sirts and Adipocyte Browningmentioning

confidence: 96%

Role of Sirtuins in Adipose Tissue Development and Metabolism

Kuryłowicz¹

2019

Adipose Tissue - An Update

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“…SIRT5 also modulates catabolism of different nutrients including glucose, fatty acids and amino acids. Several recent studies demonstrated that SIRT5 plays a regulatory role in the differentiation and function of the BAT, which is responsible for energy expenditure and combat of obesity and diabetes [74,75]. In addition to catalyzing deacetylation, SIRT5 has the enzyme activities of demalonylation, desuccinylation and deglutarylation on a number of mitochondrial proteins by removing malonyl, succinyl and glutaryl groups, respectively, from lysine residues of target proteins [12].…”

Section: Sirt5 Regulates Mitochondrial Metabolism and Insulin Sensitimentioning

confidence: 99%

“…Shuai et al showed that SIRT5 is required for the differentiation of brown adipocytes and browning of white adipocytes in vitro and in vivo [75]. SIRT5 deficiency decreases intracellular α-ketoglutarate level and leads to the accumulation of repressive histone modifications (H3K9me2 and H3K9me3) at the promoter region of Prdm16, which is a transcription factor required for the expression of brown adipocyte-specific genes [75]. However, the details of mechanism underlying SIRT5-mediated epigenetic regulation warrant further investigation.…”

Section: Sirt5 In Bat Function and Adipogenic Differentiationmentioning

confidence: 99%

Roles of Mitochondrial Sirtuins in Mitochondrial Function, Redox Homeostasis, Insulin Resistance and Type 2 Diabetes

Wang

Wei

2020

IJMS

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Mitochondria are the metabolic hubs that process a number of reactions including tricarboxylic acid cycle, β-oxidation of fatty acids and part of the urea cycle and pyrimidine nucleotide biosynthesis. Mitochondrial dysfunction impairs redox homeostasis and metabolic adaptation, leading to aging and metabolic disorders like insulin resistance and type 2 diabetes. SIRT3, SIRT4 and SIRT5 belong to the sirtuin family proteins and are located at mitochondria and also known as mitochondrial sirtuins. They catalyze NAD+-dependent deacylation (deacetylation, demalonylation and desuccinylation) and ADP-ribosylation and modulate the function of mitochondrial targets to regulate the metabolic status in mammalian cells. Emerging evidence has revealed that mitochondrial sirtuins coordinate the regulation of gene expression and activities of a wide spectrum of enzymes to orchestrate oxidative metabolism and stress responses. Mitochondrial sirtuins act in synergistic or antagonistic manners to promote respiratory function, antioxidant defense, insulin response and adipogenesis to protect individuals from aging and aging-related metabolic abnormalities. In this review, we focus on the molecular mechanisms by which mitochondrial sirtuins regulate oxidative metabolism and antioxidant defense and discuss the roles of their deficiency in the impairment of mitochondrial function and pathogenesis of insulin resistance and type 2 diabetes.

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“…Interestingly, although no concrete work has been done in keratinocytes, SIRT4 and SIRT5 have been found to regulate the differentiation of adipocytes. In one study, SIRT4 was shown to be upregulated in subcutaneous bovine adipocyte differentiation (55); while another group found that SIRT5 was necessary in the browning of subcutaneous white adipose tissue (56). These findings suggest that mitochondrial sirtuins, especially SIRT3, may be key modulators in the harmony and regulation of cellular differentiation.…”

Section: Role In Keratinocyte Differentiationmentioning

confidence: 99%

Mitochondrial Sirtuins in Skin and Skin Cancers

Ndiaye

Singh

et al. 2020

Photochem & Photobiology

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Mammalian sirtuins (SIRTs 1‐7) are a family of NAD+‐dependent deacetylases with distinct subcellular localization and biological functions that regulate various important cellular processes. Among these, SIRTs ‐3, ‐4 and ‐5 are located in the mitochondria and have been implicated in caloric restriction, oxidative stress, aging and various human diseases. Emerging evidence has found dysregulation of mitochondrial sirtuins in multiple dermatological conditions, including responses to ultraviolet radiation (UVR), suggesting their importance in maintaining skin health. In this review, we discuss the roles and implications of mitochondrial sirtuins in cutaneous cellular processes, and their emerging potential as a target for the management of skin diseases, including skin cancer. Among mitochondrial sirtuins, SIRT3 is the most studied and linked to multiple skin conditions and diseases (keratinocyte differentiation, wound healing, chronological aging, UVR and ozone response, systemic sclerosis, melanoma, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)). SIRT4 has been connected to keratinocyte differentiation, chronological aging, UVR response, alopecia, BCC and SCC. Further, SIRT5 has been associated with keratinocyte differentiation, melanoma, BCC and SCC. Overall, while there is compelling evidence for the involvement of mitochondrial sirtuins in skin, additional detailed studies are needed to understand their exact roles in skin and skin cancers.

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SIRT5 Regulates Brown Adipocyte Differentiation and Browning of Subcutaneous White Adipose Tissue

Cited by 41 publications

References 49 publications

Role of Sirtuins in Adipose Tissue Development and Metabolism

Role of Sirtuins in Adipose Tissue Development and Metabolism

Roles of Mitochondrial Sirtuins in Mitochondrial Function, Redox Homeostasis, Insulin Resistance and Type 2 Diabetes

Mitochondrial Sirtuins in Skin and Skin Cancers

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