Implication of Acyl Coenzyme A Binding Protein (ACBP) in Cushing Syndrome
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PROVIDER: PRJNA1045563 | ENA |
REPOSITORIES: ENA
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Project description:Acyl coenzyme A binding protein (ACBP), encoded by the diazepam binding protein (DBI) gene, plays a pivotal role in stimulating appetite and lipo-anabolic reactions, showing correlations with laboratory indications of metabolic syndrome in ostensibly healthy individuals. In a screening effort targeting inhibitors of ACBP/DBI expression among distinct neuroendocrine factors, we discovered that glucocorticoids induce ACBP/DBI secretion in cultured cells. In mouse models of iatrogenic Cushing syndrome, antibody-mediated neutralization of ACBP/DBI prevented the metabolic consequences of prolonged glucocorticoid administration. Our findings suggest that a surge in extracellular ACBP/DBI may mediate crucial aspects of Cushing syndrome.
2024-10-02 | GSE248672 | GEO
Project description:The plasma concentrations of acyl coenzyme A binding protein (ACBP, also known as diazepam-binding inhibitor, DBI, or ‘endozepine’) increase with age and obesity, two parameters that are also the most important risk factors for cancer. In mice bearing MCA205 fibrosarcoma, antibody mediated ACBP/DBI neutralization enhanced the anticancer T-cell response in the context of chemoimmunotherapy. T-cells infiltrating MCA205 tumors were sorted and submitting to single-cell TCR sequencing and single-cell RNA sequencing (scRNAseq) to identify the mechanisms driving this improvement.
2024-09-11 | GSE242119 | GEO
Project description:Floodings already have a nearly 60% share in the worldwide damage to crops provoked by natural disasters. Climate change will cause plants to be even more frequently exposed to oxygen limiting conditions (hypoxia) in the near future due to heavy precipitation and concomitant waterlogging or flooding events in large areas of the world. Although the homeostatic regulation of adaptive responses to low oxygen stress in plants is well described, it remained unknown by which initial trigger the molecular response to low-oxygen stress is activated. Here, we show that a hypoxia-induced decline of the ATP level of the cell reduces LONG-CHAIN ACYL-COA SYNTHETASE (LACS) activity, which leads to a shift in the composition of the acyl-CoA pool. High oleoyl-CoA levels release the transcription factor RELATED TO APETALA 2.12 (RAP2.12) from its interaction partner ACYL-COA BINDING PROTEIN (ACBP) at the plasma membrane to induce low oxygen-specific gene expression. We show that different acyl-CoAs provoke unique molecular responses revealing a novel role as cellular signalling component also in plants. In terms of hypoxia signalling, dynamic acyl-CoA levels integrate the cellular energy status into the oxygen signalling cascade with ACBP and RAP2.12 being the central hub. The conserved nature of the ACBP:RAP2.12 module in crops and the novel mechanistic understanding of how low-oxygen stress responses are initiated by oleoyl-CoA in plants provide useful leads for enhancing future food security.
2018-04-30 | GSE97186 | GEO
Project description:G-quadruplex structure (G4) is a type of DNA secondary structure that widely exists in the genomes of many organisms. G4s are believed to participate in multiple biological processes. Acyl- CoA binding protein (ACBP), a ubiquitously expressed and highly conserved protein in eukaryotic cells, plays important roles in lipid metabolism by transporting and protecting acyl-CoA esters. Here, we report the functional identification of a G4 in the promoter of the ACBP gene in silkworm and human cancer cells. We found that G4 exists as a conserved element in the promoters of ACBP genes in invertebrates and vertebrates. The BmACBP G4 bound with G4-binding protein LARK regulated BmACBP transcription, which was blocked by the G4 stabilizer pyridostatin (PDS) and G4 antisense oligonucleotides. PDS treatment with 5 th instar silkworm larvae decreased the BmACBP expression and triacylglycerides (TAG) level, resulting in reductions in fat body mass, body size and weight and growth and metamorphic rates. PDS treatment and knocking out of the HsACBP G4 in human hepatic adenocarcinoma HepG2 cells inhibited the expression of HsACBP and decreased the TAG level and cell proliferation. Altogether, our findings suggest that G4 of the ACBP genes is involved in regulation of lipid metabolism processes in invertebrates and vertebrates.
2022-05-04 | GSE201939 | GEO
Project description:Coenzyme Q10 deficiency syndrome includes a clinically heterogeneous group of mitochondrial diseases characterized by low content of CoQ10 in tissues. The only currently available treatment is supplementation with CoQ10, which improves the clinical phenotype in some patients but does not reverse established damage. Incubation with CoQ10 restored respiration and apoptotic pathways but did not affect lipid metabolism, cell growth, and undifferentiated phenotype presented by CoQ10 deficient cells. We conclude that the mitochondrial dysfunction caused byCoQ10 deficiency induces a stable survival adaptation of somatic cells from patients, thus explaining their incomplete recovery after treatment. We compared the gene expresion of human dermal fibroblast from healthy people (group 1) with fibroblast from diferent patient diagnosed with the human syndrome of coenzyme Q10 deficiency, which were treated (group 3) or not (group 2) with coenzyme Q10 to recovery ATP levels.
2013-04-05 | E-GEOD-33940 | biostudies-arrayexpress
Project description:Chronic glucocorticoids (GCs) exposure, resulting from endogenous Cushing Syndrome (CS) or prescribed GCs therapy, is associated with a high cardiometabolic burden. Moreover, previous studies have reported persistence of metabolic syndrome features after remission of hypercortisolism and in particular in visceral adipose tissue (VAT). Thus, in this study we want to analyze the transcriptomic alterations in VAT during active and cured CS and correlate these persistent gene expression changes with histone modifications induced by GCs.
2021-09-03 | GSE153934 | GEO
Project description:Chronic glucocorticoids (GCs) exposure, resulting from endogenous Cushing Syndrome (CS) or prescribed GCs therapy, is associated with a high cardiometabolic burden. Moreover, previous studies have reported persistence of metabolic syndrome features after remission of hypercortisolism and in particular in visceral adipose tissue (VAT). Thus, in this study we want to analyze the transcriptomic alterations in VAT during active and cured CS and correlate these persistent gene expression changes with changes in histone modifications induced by GCs.
2021-09-03 | GSE140126 | GEO
Project description:Coenzyme Q10 deficiency syndrome includes a clinically heterogeneous group of mitochondrial diseases characterized by low content of CoQ10 in tissues. The only currently available treatment is supplementation with CoQ10, which improves the clinical phenotype in some patients but does not reverse established damage. We analyzed the transcriptome profiles of fibroblasts from different patients irrespective of the genetic origin of the disease. These cells showed a survival genetic profile apt at maintaining growth and undifferentiated phenotype, promoting anti-apoptotic pathways, and favoring bioenergetics supported by glycolysis and low lipid metabolism. WE conclude that the mitochondrial dysfunction caused byCoQ10 deficiency induces a stable survival adaptation of somatic cells from patients. All samples in triplicate. We compare the gene expresion of human derman fibroblast to fibroblast from 4 different patient diagnosed with the human syndrome of coenzyme Q10 deficiency.
2013-04-05 | E-GEOD-33769 | biostudies-arrayexpress
Project description:During fasting, mitochondrial fatty-acid β-oxidation (mFAO) is essential for the generation of glucose by the liver. Children with a loss-of-function deficiency in the mFAO enzyme medium-chain acyl-Coenzyme A dehydrogenase (MCAD) are at serious risk of life-threatening low blood glucose levels during fasting in combination with intercurrent disease. However, a subset of these children remains asymptomatic throughout life. In MCAD-deficient (MCAD-KO) mice, glucose levels are similar to those of wild-type (WT) mice, even during fasting. We investigated if metabolic adaptations in the liver may underlie the robustness of this KO mouse. WT and KO mice were given a high- or low-fat diet and subsequently fasted. We analyzed histology, mitochondrial function, targeted mitochondrial proteomics, and transcriptome in liver tissue. Loss of MCAD led to a decreased capacity to oxidize octanoyl-CoA. This was not compensated for by altered protein levels of the short- and long-chain isoenzymes SCAD and LCAD. In the transcriptome, we identified subtle adaptations in the expression of genes encoding enzymes catalyzing CoA- and NAD(P)(H)-involving reactions and of genes involved in detoxification mechanisms. We discuss how these processes may contribute to robustness in MCAD-KO mice and potentially also in asymptomatic human subjects with a complete loss of MCAD activity.
2019-10-21 | GSE136309 | GEO
Project description:Visceral adipose tissue from human patients with Cushing was sequnced to identify novel markers of disease progression and other changes related to the disease in adipose tissue.
2023-08-30 | GSE218965 | GEO