SIRT1 suppresses adipogenesis by activating Wnt/β-catenin signaling in vivo and in vitro

Zhou, Yuanfei; Song, Tongxing; Peng, Jie; Zhou, Zheng; Wei, Hong; Zhou, Rui; Jiang, Siwen

doi:10.18632/oncotarget.12774

Cited by 73 publications

(72 citation statements)

References 42 publications

(64 reference statements)

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“…However, the main question that has to be addressed is whether Sirt1 plays any role in promoting bone formation. Without delving into the intricacies of this process, it is important to point out that it is a well‐established fact that the Wnt signaling pathway is integral to bone formation . Findings from several studies have demonstrated that there are several ways by which Sirt1 potentiates Wnt signaling, particularly in the bones .…”

Section: Discussionmentioning

confidence: 99%

“…Without delving into the intricacies of this process, it is important to point out that it is a well-established fact that the Wnt signaling pathway is integral to bone formation. (39) Findings from several studies have demonstrated that there are several ways by which Sirt1 potentiates Wnt signaling, particularly in the bones. (40)(41)(42)(43) To illustrate, Sirt1 via epigenetic silencing, downregulates the expression of Wnt antagonists such as the secreted frizzled related proteins (SFRPs) and dickkopf (Dkk) protein, leading to increased availability of the receptors for Wnt ligands and subsequently stimulation of the downstream signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

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SIRT1/HERC4 Locus Associated With Bisphosphonate-Induced Osteonecrosis of the Jaw: An Exome-Wide Association Analysis

Yang

Hamadeh

Katz

et al. 2017

Journal of Bone and Mineral Research

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Osteonecrosis of the jaw (ONJ) is a rare, but serious drug side effect, mainly associated with the use of intravenous (iv) bisphosphonates (BPs). The purpose of this study was to identify genetic variants associated with ONJ in patients of European ancestry treated with iv BPs using whole-exome sequencing (WES). The WES phase 1 included 44 multiple myeloma patients (22 ONJ cases and 22 controls) and WES phase 2 included 17 ONJ patients with solid tumors. Multivariable logistic regression analysis was performed to estimate the odds ratios (ORs) and 95% confidence intervals (CI), adjusting for age, sex, and principal components for ancestry. Meta-analysis of WES phase 1 and 2 was performed to estimate the combined ORs. In silico analyses were then performed to identify expression quantitative loci (eQTL) single-nucleotide polymorphisms (SNPs) that are in high linkage disequilibrium (LD) with the top SNPs. The associations of the potentially functional SNPs were replicated and validated in an independent case-control study of 48 patients of European ancestry treated with iv BPs (19 ONJ cases and 29 controls). The top SNPs in the exome-wide association meta-analysis were two SNPs on chromosome 10: SIRT1 SNP rs7896005 and HERC4 SNP rs3758392 with identical OR of 0.07 (0.01-0.46; p ¼ 3.83 Â 10 À5). In the in silico functional analyses, two promoter region SNPs (rs7894483 and rs3758391) were identified to be in high LD with the index SNPs and are eQTLs for SIRT1 gene in whole blood in the GTEx database. The ORs were 0.30 (0.10-0.88), 0.26 (0.12-0.55), and 0.26 (0.12-0.55) for the WES top SNP rs7896005 and two promoter SNPs rs7894483 and rs3758391, respectively, in the replication sample. In summary, we identified the SIRT1/HERC4 locus on chromosome 10 to be associated with iv BP-induced ONJ and two promoter SNPs that might be the potential genetic markers for this association.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

SIRT1/HERC4 Locus Associated With Bisphosphonate-Induced Osteonecrosis of the Jaw: An Exome-Wide Association Analysis

Yang

Hamadeh

Katz

et al. 2017

Journal of Bone and Mineral Research

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“…Adipocyte-specific Sirt1 deletion increased the adipogenic capacity of WAT in mice in response to chronic HFD as demonstrated by white adipocyte hyperplasia and hyperacetylation mediated activation of Ppar γ [115], and increased WAT mass [101], [115] even under normal conditions. In agreement, mouse embryonic fibroblasts derived from mice homo- or heterozygous for Sirt1 deletion, were shown to possess higher adipogenic capacity in cell culture [116], [117]. By contrast, treatment with pharmacological SIRT1 activators decreases WAT mass during HFD [71], [89], [90].…”

Section: Sirts and Parps In Adipose Tissue Function In Basal And Obesmentioning

confidence: 62%

“…In 3T3-L1 adipocytes genetic or pharmacological Sirt1 inhibition increased the expression of inflammatory cytokines upon tumor necrosis factor 1 alpha stimulation, whereas Sirt1 activation had the opposite effect [133]. In agreement, genetic or antisense oligonucleotide mediated Sirt1 deficiency in rodents leads to elevated inflammation characterized by increased macrophage infiltration and mRNA expression of inflammatory cytokines in WAT under normal [107] and HFD conditions [101], [115], [117], [134]. However, during long-term HFD adipocyte specific Sirt1 deletion reduced WAT inflammation in contrast to the other findings [115].…”

Section: Sirts and Parps In Adipose Tissue Function In Basal And Obesmentioning

confidence: 69%

Adipose tissue NAD+-homeostasis, sirtuins and poly(ADP-ribose) polymerases -important players in mitochondrial metabolism and metabolic health

et al. 2017

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Obesity, a chronic state of energy overload, is characterized by adipose tissue dysfunction that is considered to be the major driver for obesity associated metabolic complications. The reasons for adipose tissue dysfunction are incompletely understood, but one potential contributing factor is adipose tissue mitochondrial dysfunction. Derangements of adipose tissue mitochondrial biogenesis and pathways associate with obesity and metabolic diseases. Mitochondria are central organelles in energy metabolism through their role in energy derivation through catabolic oxidative reactions. The mitochondrial processes are dependent on the proper NAD+/NADH redox balance and NAD+ is essential for reactions catalyzed by the key regulators of mitochondrial metabolism, sirtuins (SIRTs) and poly(ADP-ribose) polymerases (PARPs). Notably, obesity is associated with disturbed adipose tissue NAD+ homeostasis and the balance of SIRT and PARP activities. In this review we aim to summarize existing literature on the maintenance of intracellular NAD+ pools and the function of SIRTs and PARPs in adipose tissue during normal and obese conditions, with the purpose of comprehending their potential role in mitochondrial derangements and obesity associated metabolic complications. Understanding the molecular mechanisms that are the root cause of the adipose tissue mitochondrial derangements is crucial for developing new effective strategies to reverse obesity associated metabolic complications.

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“…Furthermore, the murine SIRT1 knockout repressed the generation of adipose tissue34 and glucose modulation35 . BMMs were transfected for 24 h with miR-506 inhibitor prior to treatment with RANKL and EX.…”

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confidence: 99%

MicroRNA‐506 upregulation contributes to sirtuin 1 inhibition of osteoclastogenesis in bone marrow stromal cells induced by TNF‐α treatment

Shu

Miao

et al. 2019

Cell Biochemistry & Function

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As a deacetylase relying on NAD, sirtuin 1 (SIRT1) has been proven to inhibit osteoclastogenesis directly by repressing reactive oxygen species (ROS) production and TRPV1 channel stimulation modulated by TNF-α. MicroRNAs do not have coding functions, but they influence the expression of particular genes after transcription.Nevertheless, the current understanding of the impact of SIRT1 on osteoclastogenesis is insufficient. Our research explored whether and how miRNAs contributed to osteoclast differentiation modulated by SIRT1 in vitro. In osteoclastogenesis induced by RANKL in bone marrow-derived macrophages (BMMs), repression of SIRT1 expression and enhancement of miR-506 expression were discovered. Transfection with an miR-506 inhibitor repressed miR-506 concentration in BMMs treated with RANKL. Additional research revealed that BMMs with repressed miR-506 treated with RANKL displayed phenotypes with suppressed osteoclastogenesis, as demonstrated by TRAP staining, reduced function, decreased expression of osteoclast markers and correlated genes, and reduced multinuclear cell quantity. Bioinformatics prediction outcomes and the dual-luciferase reporter test suggested that miR-506 targeted the SIRT1 3′-UTR for silencing. Decreased miR-506 in BMMs induced by RANKL caused SIRT1 upregulation. Additionally, treatment with EX-527 (SIRT1 repressor) or SIRT1 silencing attenuated repression caused by miR-506 depletion in BMMs treated with RANKL. Furthermore, TNF-α was repressed via miR-506 inhibition but was enhanced following EX-527 incubation as well as SIRT1 depletion.TRPV1 channel stimulation and ROS generation, which was related to osteoclastogenesis, were reduced via miR-506 depletion. miR-506 modulated osteoclastogenesis by targeting SIRT1 expression in part through modulation of the TRPV1 channel, ROS production, and TNF-α. KEYWORDSbone marrow-derived macrophages, miR-506, osteoclastogenesis, reactive oxygen species, sirtuin 1, TNF-α, transient receptor potential vanilloid 1 Shu Yan and Lujie Miao contributed equally to this work and should be considered as equal first coauthors.

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SIRT1 suppresses adipogenesis by activating Wnt/β-catenin signaling in vivo and in vitro

Cited by 73 publications

References 42 publications

SIRT1/HERC4 Locus Associated With Bisphosphonate-Induced Osteonecrosis of the Jaw: An Exome-Wide Association Analysis

SIRT1/HERC4 Locus Associated With Bisphosphonate-Induced Osteonecrosis of the Jaw: An Exome-Wide Association Analysis

Adipose tissue NAD+-homeostasis, sirtuins and poly(ADP-ribose) polymerases -important players in mitochondrial metabolism and metabolic health

MicroRNA‐506 upregulation contributes to sirtuin 1 inhibition of osteoclastogenesis in bone marrow stromal cells induced by TNF‐α treatment

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