Oleic acid increases the transcriptional activity of FoxO1 by promoting its nuclear translocation and β-catenin binding in pancreatic β-cells

Jazurek-Ciesiolka, Magdalena; Janikiewicz, Justyna; Dobrzyń, Paweł; Dziewulska, Anna; Koziński, Kamil; Dobrzyń, Agnieszka

doi:10.1016/j.bbadis.2019.06.018

Cited by 9 publications

(5 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…104 Oxidative stress or lipid overload stimulates forkhead box class O (FoxO) target gene (p21 cip1α , p27, superoxide dismutase 2, cystathionine γ-lyase, aquaporin 1, and aldehyde dehydrogenase) expression by redirecting βcatenin from the TCF/LEF complex to FoxO and limits the expression of canonical WNT targets (c-Myc and Axin2), providing a mechanism of the antioxidant response. [105][106][107][108] Interestingly, oxidative stress inhibits Na v 1.5 channel expression in HL1 cardiomyocytes via direct βcatenin F I G U R E 2 Noncanonical nuclear βcatenin partners in cardiomyocytes. βcatenin interacts with different TFs and regulates gene expression, depending on the cellular context.…”

Section: Noncanonical Nuclear Partners Of βCatenin In Cardiomyocytesmentioning

confidence: 99%

“…109,110 Mechanistically, oxidative stress leads to a decrease in Akt-mediated FoxO phosphorylation but an increase in JNK-mediated FoxO phosphorylation, which leads to an enhanced interaction with βcatenin. 105,106 Additionally, the FoxO/β-catenin complex is stabilized by ICAT, an inhibitor of the βcatenin interaction with TCF/ LEF, providing a molecular switch between different βcatenin-containing transcriptional complexes. 111 βcatenin forms a complex with yes-associated protein (YAP) on the promoters of the Sox2 and Snai2 genes and supports heart growth.…”

Section: Noncanonical Nuclear Partners Of βCatenin In Cardiomyocytesmentioning

confidence: 99%

“…Interestingly, oxidative stress inhibits Na v 1.5 channel expression in HL1 cardiomyocytes via direct β‐catenin and FoxO‐1 binding to the promoter of the Scn5a gene, suggesting their cooperative response to oxidative damage 109,110 . Mechanistically, oxidative stress leads to a decrease in Akt‐mediated FoxO phosphorylation but an increase in JNK‐mediated FoxO phosphorylation, which leads to an enhanced interaction with β‐catenin 105,106 . Additionally, the FoxO/β‐catenin complex is stabilized by ICAT, an inhibitor of the β‐catenin interaction with TCF/LEF, providing a molecular switch between different β‐catenin‐containing transcriptional complexes 111 …”

Section: Canonical Wnt Signaling Pathway: Main Components and Stepsmentioning

confidence: 99%

See 2 more Smart Citations

WNT/β‐catenin pathway is a key regulator of cardiac function and energetic metabolism

et al. 2023

Self Cite

View full text Add to dashboard Cite

The WNT/β‐catenin pathway is a master regulator of cardiac development and growth, and its activity is low in healthy adult hearts. However, even this low activity is essential for maintaining normal heart function. Acute activation of the WNT/β‐catenin signaling cascade is considered to be cardioprotective after infarction through the upregulation of prosurvival genes and reprogramming of metabolism. Chronically high WNT/β‐catenin pathway activity causes profibrotic and hypertrophic effects in the adult heart. New data suggest more complex functions of β‐catenin in metabolic maturation of the perinatal heart, establishing an adult pattern of glucose and fatty acid utilization. Additionally, low basal activity of the WNT/β‐catenin cascade maintains oxidative metabolism in the adult heart, and this pathway is reactivated by physiological or pathological stimuli to meet the higher energy needs of the heart. This review summarizes the current state of knowledge of the organization of canonical WNT signaling and its function in cardiogenesis, heart maturation, adult heart function, and remodeling. We also discuss the role of the WNT/β‐catenin pathway in cardiac glucose, lipid metabolism, and mitochondrial physiology.

show abstract

Section: Noncanonical Nuclear Partners Of βCatenin In Cardiomyocytesmentioning

confidence: 99%

Section: Noncanonical Nuclear Partners Of βCatenin In Cardiomyocytesmentioning

confidence: 99%

Section: Canonical Wnt Signaling Pathway: Main Components and Stepsmentioning

confidence: 99%

See 1 more Smart Citation

WNT/β‐catenin pathway is a key regulator of cardiac function and energetic metabolism

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…Noteworthy, palmitate enhances some of the effects of SCD1 deficiency in β-cells [ 22 , 37 ]. Furthermore, since oleate can overcome some of the effects of SCD1 deficiency in hepatocytes [ 38 ], and given the important role of oleate in regulation of β-cell function [ 39 ], it is possible that the effects of SCD1 deficiency in β-cells may be mediated by oleate. However, more studies are needed to address this issue.…”

Section: Discussionmentioning

confidence: 99%

Stearoyl-CoA Desaturase 1 Activity Determines the Maintenance of DNMT1-Mediated DNA Methylation Patterns in Pancreatic β-Cells

Dobosz

Janikiewicz

Borkowska

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Metabolic stress, such as lipotoxicity, affects the DNA methylation profile in pancreatic β-cells and thus contributes to β-cell failure and the progression of type 2 diabetes (T2D). Stearoyl-CoA desaturase 1 (SCD1) is a rate-limiting enzyme that is involved in monounsaturated fatty acid synthesis, which protects pancreatic β-cells against lipotoxicity. The present study found that SCD1 is also required for the establishment and maintenance of DNA methylation patterns in β-cells. We showed that SCD1 inhibition/deficiency caused DNA hypomethylation and changed the methyl group distribution within chromosomes in β-cells. Lower levels of DNA methylation in SCD1-deficient β-cells were followed by lower levels of DNA methyltransferase 1 (DNMT1). We also found that the downregulation of SCD1 in pancreatic β-cells led to the activation of adenosine monophosphate-activated protein kinase (AMPK) and an increase in the activity of the NAD-dependent deacetylase sirtuin-1 (SIRT1). Furthermore, the physical association between DNMT1 and SIRT1 stimulated the deacetylation of DNMT1 under conditions of SCD1 inhibition/downregulation, suggesting a mechanism by which SCD1 exerts control over DNMT1. We also found that SCD1-deficient β-cells that were treated with compound c, an inhibitor of AMPK, were characterized by higher levels of both global DNA methylation and DNMT1 protein expression compared with untreated cells. Therefore, we found that activation of the AMPK/SIRT1 signaling pathway mediates the effect of SCD1 inhibition/deficiency on DNA methylation status in pancreatic β-cells. Altogether, these findings suggest that SCD1 is a gatekeeper that protects β-cells against the lipid-derived loss of DNA methylation and provide mechanistic insights into the mechanism by which SCD1 regulates DNA methylation patterns in β-cells and T2D-relevant tissues.

show abstract

“…Molecular detailing showed transcription factor forkhead box protein O1 (FOXO1) to translocate to the nucleus under metabolic stress conditions and inhibit the matured β-cells undergoing reprograming to the progenitor state. FOXO1 also rescues key parameters related to diabetes like decreased β-cell mass and function (Talchai et al, 2012, Kitamura et al, 2005, Fiori et al, 2013, Jazurek-Ciesiolka et al, 2019. Injury models such as pancreatic ductal ligation or pancreatectomy conditions have been shown to drive the dedifferentiation of β-cells and the mechanism has been attributed to the signalling of TGFβ secreted by the immune cells (Xiao X et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Deubiquitinase USP1 influences the dedifferentiation of mouse pancreatic β-cells

Francis

Sheshadri

Prasanna

et al. 2022

Preprint

View full text Add to dashboard Cite

Diabetes is a metabolic disease caused majorly due to loss of insulin secreting β-cells. Along with apoptosis, recent reports revealed dedifferentiation to be the added reason for the reduced β-cell mass. The Ubiquitin Proteasome system comprising of E3 ligase and deubiquitinases (DUBs) control several key aspects of pancreatic β-cell functions. The role of deubiquitinases in orchestrating the dedifferentiation process in several cancers have been well deciphered, but its role in dedifferentiation of pancreatic β-cells remains elusive. In this study, screening for key DUBs that regulate dedifferentiation, identified USP1 to be specifically involved in the process. Inhibition of USP1 either by genetic intervention or small molecule inhibitor ML323 restored epithelial phenotype of β-cells, but not with inhibition of other DUBs. Conversely overexpression of USP1 was sufficient to dedifferentiate β-cells, even in absence of dedifferentiation inducing cues. Mechanistic insight showed USP1 to probably mediate its effect via modulating the expression of Inhibitor of Differentiation (ID) 2. Further, in an in vivo streptozotocin (STZ) induced dedifferentiation mouse model system, treatment with ML323 rescued the hyperglycaemic state. Overall, this study assigns a novel role to USP1 in dedifferentiation of β-cells and its inhibition may have a therapeutic application of reducing the β-cell loss during diabetes.

show abstract

Oleic acid increases the transcriptional activity of FoxO1 by promoting its nuclear translocation and β-catenin binding in pancreatic β-cells

Cited by 9 publications

References 60 publications

WNT/β‐catenin pathway is a key regulator of cardiac function and energetic metabolism

WNT/β‐catenin pathway is a key regulator of cardiac function and energetic metabolism

Stearoyl-CoA Desaturase 1 Activity Determines the Maintenance of DNMT1-Mediated DNA Methylation Patterns in Pancreatic β-Cells

Deubiquitinase USP1 influences the dedifferentiation of mouse pancreatic β-cells

Contact Info

Product

Resources

About