Succinate diminishes biological activity and mitochondrial function of human adipose-derived stem cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1152262 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30362764_1.fastq.gz | Fastqsanger.gz | |||
| SRR30362764_2.fastq.gz | Fastqsanger.gz | |||
| SRR30362765_1.fastq.gz | Fastqsanger.gz | |||
| SRR30362765_2.fastq.gz | Fastqsanger.gz | |||
| SRR30362766_1.fastq.gz | Fastqsanger.gz |
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Project description:Alterations in succinate levels have been associated with various metabolic and inflammatory diseases. However, little is currently known about whether adipose-derived stem cells (ADSCs) undergo changes when exposed to succinate. Here, we investigate the biological properties, mitochondrial function and immunophenotype of ADSCs treated with succinate. We observed that reduced biological activity of ADSCs following by succinate stimulated. Of note, succinate treated-ADSCs exhibit mitochondrial dysfunctions, including increased mitochondrial fragments, decreased mitochondrial mass, increased ROS production, reduced Oxidative phosphorylation (OXPHOS). Furthermore, transcriptome analysis revealed that the downregulation of genes involved in cell proliferation, OXPHOS and metabolism, whereas the signaling pathways related to cancer, apoptosis, inflammation were upregulated upon succinate treatment. The findings indicate that ADSCs exposed to succinate exhibit signs of mitochondrial dysfunction, inflammation, and a significant decrease in biological activity.
2024-08-30 | GSE275624 | GEO
Project description:The concept of “signaling metabolites” in the control of metabolic homeostasis is gaining traction. The Krebs cycle substrate succinate, a pleiotropic metabolite that acts akin to hormones and cytokines through succinate receptor 1 (SUCNR1, also known as GPR91), is one example of this new class of metabolites. SUCNR1 has a broad expression and is highly abundant in white adipose tissue. It was a general assumption that SUCNR1 is functionally inactive in healthy tissues, and for many years, SUCNR1 was explored from an immune perspective, mainly in inflammatory-related conditions, particularly those associated with chronic hypersuccinemia. Recent studies, however, indicate that extracellular levels of succinate transiently increase in response to physiological changes such as exercise, cold exposure, or food ingestion. Succinate thus emerges as a reporter of both tissue stress and metabolism, raising the possibility of its involvement in additional metabolic functions as a hormone-like metabolite. Indeed, it is conceivable that "succinate sensing" by SUCNR1 may be part of the metabolite-sensing machinery that governs energy homeostasis. To better understand the effect of the adipocyte Sucnr1 deletion on adipose tissue, we selectively inactivated Sucnr1 in murine adipocytes and profiled the transcription state of epididymal white adipose tissue from adipocyte cell-specific Sucnr1 knockout mice (Ad-Sucnr1 KO) and control Sucnr1fl/fl mice.
2023-03-27 | GSE200749 | GEO
Project description:In Crohn’s disease (CD), microbe-host interactions are altered, with changes in microbial’s communities and barrier defects leading to translocation of microbes to surrounding adipose tissue (AT). We evaluated the presence of beige AT depots in CD and questioned whether succinate and/or bacterial translocation promotes white-to-beige transition in adipocytes.
2022-09-14 | PXD030520 | Pride
Project description:Uptake of circulating succinate by brown adipose tissue (BAT) and beige fat elevates whole-body energy expenditure, counteracts obesity, and antagonizes systemic tissue inflammation in mice. The plasma membrane transporters that facilitate succinate uptake in these adipocytes remain undefined. Here we elucidate a mechanism underlying succinate import into BAT via monocarboxylate transporters (MCTs). We show that succinate transport is strongly dependent on the proportion of it present in the monocarboxylate form. MCTs facilitate monocarboxylate succinate uptake, which is promoted by alkalinization of the cytosol driven by adrenoreceptor stimulation. In brown adipocytes, we show that MCT1 primarily facilitates succinate import. In mice, we show that both acute pharmacological inhibition of MCT1 and congenital depletion of MCT1, decrease succinate uptake into BAT and consequent catabolism. In sum, we define a mechanism of succinate uptake in BAT that underlies its protective activity in mouse models of metabolic disease.
2024-01-10 | PXD048056 | Pride
Project description:In the present study, we discovered an unexpected interplay between immunometabolism and antiviral immunity. Profiling of human bronchial epithelial BEAS-2B cells was performed using Agilent’s SurePrint G3 human gene expression microarray kit. A single-color design provided two types of comparison: (i) IAV-infected versus mock-infected cells, and (ii) succinate-treated infected cells versus mock-infected cells.
2022-02-17 | E-MTAB-10031 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE25323: Biological Aging and Circadian Mechanisms in Murine Brown Adipose Tissue, Inguinal White Adipose Tissue, and Liver (Nov 2009 dataset) GSE25324: Biological Aging and Circadian Mechanisms in Murine Brown Adipose Tissue, Inguinal White Adipose Tissue, and Liver (Jan 2010 dataset) Refer to individual Series
2012-03-15 | E-GEOD-25325 | biostudies-arrayexpress
Project description:Drug resistance is vital for the poor prognosis of acute myeloid leukemia (AML) patients, but the underlying mechanism remains poorly understood. Given the unique microenvironment of bone marrow, we reasoned that drug resistance of AML might rely on distinct microenvironment-associated metabolic processes. Here, we identified SDH deficiency and over-cumulative succinate as typical features in AML, with a marked function in causing the resistance of AML cells to a wide range of anti-cancer therapies. Mechanistically, succinate promoted the accumulation of oncogenic proteins in a manner that precedes transcriptional activation. This function was mediated by succinate-triggered upregulation of UBC12 phosphorylation, which impaired its E2 function in cullins neddylation. Notably, decreasing succinate levels by fludarabine could effectively restore the drug sensitivity of SDH-deficient AML PDX. Together, we uncover a novel function of succinate in driving drug resistance by regulating p-UBC12/cullin activity, and indicate reshaping succinate metabolism as a promising treatment for SDH-deficient AML.
2024-08-27 | GSE247623 | GEO
Project description:Analysis of gene expression in Pseudonocardia dioxanivorans strain CB1190 during growth on THF (tetradhydrofuran) or succinate, and re-analysis of GSE33197 published expression data. Two new treatments, based on carbon/energy source used for growth: THF and succinate. Three previously published treatments (pyruvate, dioxane, and glycolate) from GEO Series GSE33197 were also reanalyzed. Triplicate microarrays (biological replicates) were prepared for each treatment. Gene expression changes were compared directly between the new treatments (THF vs. succinate) and to previously published data during growth on pyruvate (GEO accession numbers GSM821862-GSM821864) in order to yield THF vs. pyruvate and succinate vs. pyruvate contrasts. Included as part of the re-analysis of GSE33197 were data from dioxane and glycolate treatments (GSM821865-GSM821870). The complete dataset representing: (1) the THF- and succinate-treated CB1190 Samples and (2) the pyruvate-, dioxane- and glycolate-treated CB1190 Samples from Series GSE33197 (re-processed using RMA), is linked below as a supplementary file (GSE48814_complete_data.txt).
2013-07-12 | E-GEOD-48814 | biostudies-arrayexpress
Project description:Drug resistance is vital for the poor prognosis of acute myeloid leukemia (AML) patients, but the underlying mechanism remains poorly understood. Given the unique microenvironment of bone marrow, we reasoned that drug resistance of AML might rely on distinct microenvironment-associated metabolic processes. Here, we identified SDH deficiency and over-cumulative succinate as typical features in AML, with a marked function in causing the resistance of AML cells to a wide range of anti-cancer therapies. Mechanistically, succinate promoted the accumulation of oncogenic proteins in a manner that precedes transcriptional activation. This function was mediated by succinate-triggered upregulation of UBC12 phosphorylation, which impaired its E2 function in cullins neddylation. Notably, decreasing succinate levels by fludarabine could effectively restore the drug sensitivity of SDH-deficient AML PDX. Together, we uncover a novel function of succinate in driving drug resistance by regulating p-UBC12/cullin activity, and indicate reshaping succinate metabolism as a promising treatment for SDH-deficient AML.
2024-08-28 | PXD053722 | Pride
Project description:Drug resistance is vital for the poor prognosis of acute myeloid leukemia (AML) patients, but the underlying mechanism remains poorly understood. Given the unique microenvironment of bone marrow, we reasoned that drug resistance of AML might rely on distinct microenvironment-associated metabolic processes. Here, we identified SDH deficiency and over-cumulative succinate as typical features in AML, with a marked function in causing the resistance of AML cells to a wide range of anti-cancer therapies. Mechanistically, succinate promoted the accumulation of oncogenic proteins in a manner that precedes transcriptional activation. This function was mediated by succinate-triggered upregulation of UBC12 phosphorylation, which impaired its E2 function in cullins neddylation. Notably, decreasing succinate levels by fludarabine could effectively restore the drug sensitivity of SDH-deficient AML PDX. Together, we uncover a novel function of succinate in driving drug resistance by regulating p-UBC12/cullin activity, and indicate reshaping succinate metabolism as a promising treatment for SDH-deficient AML.
2024-08-28 | PXD047175 | Pride