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Succinate diminishes biological activity and mitochondrial function of human adipose-derived stem cells

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE275624 | GEO | 2024/08/30

REPOSITORIES: GEO

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Succinate diminishes biological activity and mitochondrial function of human adipose-derived stem cells

Project description:Succinate diminishes biological activity and mitochondrial function of human adipose-derived stem cells

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Ileum/colon treated with succinate

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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.

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Pseudonocardia dioxanivorans strain CB1190 during growth on THF or succinate

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).

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