Sirtuins in glucose and lipid metabolism

Ye, Xin; Li, Meiting; Hou, Tianyun; Gao, Tian; Zhu, Wei‐Guo; Yang, Yang

doi:10.18632/oncotarget.12157

Cited by 161 publications

(132 citation statements)

References 106 publications

Supporting

Mentioning

126

Contrasting

Unclassified

Order By: Relevance

“…In the present study, Glut1 was upregulated in Trp53(-/-) kidneys as part of the Sirtuin 6 pathway. Sirtuin proteins regulate both glucose and lipid metabolism; and act on switching the two forms of metabolism [88,91]. Given that p53 plays a role in glucose metabolism by downregulating the expression of glucose transporters (e.g., GLUT1, GLUT4) [92], it may be that a Trp53(-/-) genotype confers a deregulation in Glut1 expression and drives glycolysis.…”

Section: Discussionmentioning

confidence: 99%

The Impact of p53 on Aristolochic Acid I-Induced Gene Expression In Vivo

Sborchia

Keun

Phillips

et al. 2019

IJMS

View full text Add to dashboard Cite

Exposure to aristolochic acid (AA) is linked to kidney disease and urothelial cancer in humans. The major carcinogenic component of the AA plant extract is aristolochic acid I (AAI). The tumour suppressor p53 is frequently mutated in AA-induced tumours. We previously showed that p53 protects from AAI-induced renal proximal tubular injury, but the underlying mechanism(s) involved remain to be further explored. In the present study, we investigated the impact of p53 on AAI-induced gene expression by treating Trp53(+/+), Trp53(+/-), and Trp53(-/-) mice with 3.5 mg/kg body weight (bw) AAI daily for six days. The Clariom™ S Assay microarray was used to elucidate gene expression profiles in mouse kidneys after AAI treatment. Analyses in Qlucore Omics Explorer showed that gene expression in AAI-exposed kidneys is treatment-dependent. However, gene expression profiles did not segregate in a clear-cut manner according to Trp53 genotype, hence further investigations were performed by pathway analysis with MetaCore™. Several pathways were significantly altered to varying degrees for AAI-exposed kidneys. Apoptotic pathways were modulated in Trp53(+/+) kidneys; whereas oncogenic and pro-survival pathways were significantly altered for Trp53(+/-) and Trp53(-/-) kidneys, respectively. Alterations of biological processes by AAI in mouse kidneys could explain the mechanisms by which p53 protects from or p53 loss drives AAI-induced renal injury in vivo.

show abstract

Section: Discussionmentioning

confidence: 99%

The Impact of p53 on Aristolochic Acid I-Induced Gene Expression In Vivo

Sborchia

Keun

Phillips

et al. 2019

IJMS

View full text Add to dashboard Cite

show abstract

“…Apart from the regulation of PPARα-related pathways, sirt1 may influence FA metabolism via downregulation of sterol regulatory element-binding proteins 1 and 2 (SREBP-1 and SREBP-2) transcription factors. sirt1 overexpression or its activation by, e.g., resveratrol (RSV), prevents cleavage-induced activation of SERBs and their translocation to the nucleus where they promote transcription of genes crucial for sterol biosynthesis [34]. sirt1 KO mice have lower SREBP-1 mRNA levels in the liver that correlates with decreased serum triglyceride concentrations [35].…”

Section: Sirts In Lipid Metabolismmentioning

confidence: 99%

Role of Sirtuins in Adipose Tissue Development and Metabolism

Kuryłowicz¹

2019

Adipose Tissue - An Update

View full text Add to dashboard Cite

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...

show abstract

“…Sirtuins (SIRTs) are a family of enzymes with crucial roles in the control of cellular metabolism (133). Continuously increasing evidence indicates that sirtuins are needed for metabolic adaptations in energy homeostasis in response to changes in nutritional status.…”

Section: Introductionmentioning

confidence: 99%