Reduced lipolysis is a common lipid accumulation mechanism for different subtypes of lipomas
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ABSTRACT:
PROVIDER: PRJNA591799 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10533514_1.fastq.gz | Fastqsanger.gz | |||
| SRR10533514_2.fastq.gz | Fastqsanger.gz | |||
| SRR10533515_1.fastq.gz | Fastqsanger.gz | |||
| SRR10533515_2.fastq.gz | Fastqsanger.gz | |||
| SRR10533516_1.fastq.gz | Fastqsanger.gz |
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Project description:We used RNA-seq to inquire gene expression profiles of lipomas with HMGA2-fusions and without gene fusions. We demonstrate that HMGA2-fusions lipomas are a specific subtype and that the common shared lipid accumulation mechanism is a reduction in lipolysis, with most gene-dysregulations leading to a reduced cAMP in the adipocyte.
2020-05-25 | GSE141027 | GEO
Project description:BackgroundElucidation of lipid metabolism and accumulation mechanisms is of paramount importance to understanding obesity and unveiling therapeutic targets. In vitro cell models have been extensively used for these purposes, yet, they do not entirely reflect the in vivo setup. Conventional lipomas, characterized by the presence of mature adipocytes and increased adipogenesis, could overcome the drawbacks of cell cultures. Also, they have the unique advantage of easily accessible matched controls in the form of subcutaneous adipose tissue (SAT) from the same individual. We aimed to determine whether lipomas are a good model to understand lipid accumulation.MethodsWe histologically compared lipomas and control SAT, followed by assessment of the lipidome using high-resolution 1H NMR spectroscopy and ESI-IT mass spectrometry. RNA-sequencing was used to obtain the transcriptome of lipomas and the matched SAT.ResultsWe found a significant increase of small-size (maximal axis < 70 µm) and very big (maximal axis > 150 µm) adipocytes within lipomas. This suggests both enhanced adipocyte proliferation and increased lipid accumulation. We further show that there is no significant change in the lipid composition compared to matched SAT. To better delineate the pathophysiology of lipid accumulation, we considered two groups with different genetic backgrounds: (1) lipomas with HMGA2 fusions and (2) without gene fusions. To reduce the search space for genes that are relevant for lipid pathophysiology, we focused on the overlapping differentially expressed (DE) genes between the two groups. Gene Ontology analysis revealed that DE genes are enriched in pathways related to lipid accumulation.ConclusionsWe show that the common shared lipid accumulation mechanism in lipoma is a reduction in lipolysis, with most gene dysregulations leading to a reduced cAMP in the adipocyte. Superficial lipomas could thus be used as a model for lipid accumulation through altered lipolysis as found in obese patients.
| S-EPMC7906903 | biostudies-literature
Project description:Noncanonical lipolysis induced by inflammatory cytokines or toll-like receptor ligands is required for the regulation of inflammation during endotoxemia and sepsis. Canonical lipolysis induced by catecholamines declines during aging, but the extent to which the noncanonical pathway of lipolysis is active during aging remains unknown. The immune compartment of visceral white adipose tissue (vWAT) changes during aging, including an expansion of lymphocytes, pro-inflammatory macrophage polarization, and an increase in chronic low-grade inflammation, all of which influence canonical lipolysis in old vWAT. Therefore, we aimed to define the extent to which immune cells from older hosts influence noncanonical lipolysis induced by sepsis. Here we show that models of polymicrobial sepsis and lipopolysaccharide (LPS)-induced endotoxemia induce vWAT lipolysis in young mice but fail to activate lipolytic pathways in vWAT from old mice. Characterization of vWAT B cells revealed an accumulation of dysfunctional B1 B cells and an amplified inflammatory signature induced by LPS in old B1 B cells compared to old B2 B cells. Short term depletion of B2 B cells from old mice and adoptive transfer of peritoneal B cells from old mice into young recipient mice were insufficient to alter LPS-stimulated lipolysis. However, life-long deficiency of B cells increased LPS-stimulated lipolysis, suggesting the suppressive role of B cells may be indirect and requires other cell types. Pro-inflammatory macrophages and NLRP3 inflammasome activation were significantly reduced in the old B cell knockout mice. These data collectively reveal a decline in noncanonical lipolysis in vWAT during aging that is regulated by resident immune cells. Additionally, our study suggests the B cell-macrophage signaling axis may offer new approaches to resolve metabolic dysfunction in aged vWAT and attenuate septic severity in older individuals.
2024-03-18 | GSE250371 | GEO
Project description:As cows progress from pregnancy to lactation, the adipose tissues (AT) undergo adaptations characterized by the mobilization of free fatty acids (FFA) through lipolysis to address energy deficiencies. Typically, in clinically healthy cows, the intensity of lipolysis decreases during lactation. However, when the release of FFA surpasses tissue requirements, it leads to the accumulation of lipid-derived products, heightening the susceptibility of cows to metabolic and infectious diseases. A second factor correlated to disease incidence in dairy cows is the presence of bacterial endotoxins in blood. The last is implicated in AT lipolysis and dysfunction in mammals. However, the mechanisms by which endotoxin activates lipolysis and affects the formation of lipid derived products in bovine adipocyte remains unknown. We hypothesize that endotoxin triggers AT dysfunction by increasing the synthesis and release of lipid-derived products with proinflammatory potential. Preadipocytes were obtained from subcutaneous AT of multiparous Holstein cows (n=9). Adipogenesis was induced for 7 d and cells were incubated with endotoxin [lipopolysaccharide 1µg/mL (LPS)] for up to 7 h. Beta-adrenergic receptor agonist isoproterenol (ISO; 1 µM) was used as an activator of canonical lipolysis. The antilipolytic effect of insulin was evaluated alone or in combination with LPS. Lipolysis was evaluated by the release of glycerol in the media. RNA from adipocytes was sequenced in Illumina NextSeqData, and Differential Expressed Genes (DEG) identified. Enrichment and network analyses were performed in Ingenuity Pathways (IPA). Our findings provide evidence supporting the higher abundance of lipid-derived products with proinflammatory activity and dysfunction related to inflammatory activation.
2024-05-20 | GSE267141 | GEO
Project description:The Wnt/Wingless signaling pathway plays critical roles in metazoan development and energy metabolism, but its involvement in lipid mobilization has remained unclear. Here, we report that canonical Wnt/Wg signaling reduces lipid accumulation in both larval and adult adipocytes, as well as cultured S2R+ cells, in Drosophila. This reduction occurs through promoting lipolysis while concurrently repressing lipogenesis and fatty acid β-oxidation. Leveraging RNA-sequencing and CUT&RUN assays, we have identified a set of Wnt target genes responsible for intracellular lipid homeostasis. Notably, active Wnt signaling directly represses the transcription of these genes, resulting in decreased triglyceride accumulation in lipid droplets, increased lipolysis, and reduced fatty acid β-oxidation. These changes lead to elevated free fatty acids and reduced triglyceride accumulation in adipocytes with active Wnt signaling. Conversely, downregulation of Wnt signaling in the fat body promotes triglyceride accumulation in both larval and adult stages. The attenuation of Wnt signaling also increases the expression of specific lipid metabolism-related genes in larval adipocytes, wing discs, and adult intestines. Collectively, our findings suggest that Wnt signaling-induced transcriptional repression plays an important role in regulating lipid homeostasis by enhancing lipolysis while simultaneously suppressing lipogenesis and fatty acid β-oxidation processes.
2024-06-18 | GSE264356 | GEO
Project description:<p>The central nervous system has been implicated in the age-induced reduction in adipose tissue lipolysis. SLC7A14 is a lysosomal membrane protein highly expressed in the brain. Herein, we investigated the possible role of hypothalamic SLC7A14 in the age-induced lipolysis reduction. In this study, we demonstrated the expression of SLC7A14 was reduced in proopiomelanocortin (POMC) neurons of aged mice. Overexpression of SLC7A14 in POMC neurons alleviated the age-induced reduction in white adipose tissue (WAT) lipolysis, whereas SLC7A14 deletion mimicked the age-induced lipolysis impairment. Moreover, POMC SLC7A14 regulated WAT lipolysis independently of sympathetic nerves in WAT. Metabolomics analysis revealed that POMC SLC7A14 increased the primary bile acid taurochenodeoxycholic acid (TCDCA) content, which mediated the SLC7A14 knockout- or age-induced WAT lipolysis impairment. Furthermore, SLC7A14-increased TCDCA content is dependent on intestinal apical sodium-dependent bile acid transporter (ASBT), which is regulated by intestinal sympathetic afferent nerves. Finally, SLC7A14 regulated the intestinal sympathetic afferent nerves by inhibiting mTORC1 signaling through inhibiting TSC1 phosphorylation. Collectively, our study suggests the function for central SLC7A14 and an upstream mechanism for the mTORC1 signaling pathway. Moreover, our data provides insights into the brain-gut-adipose tissue crosstalk in age-induced lipolysis impairment.</p>
2024-07-23 | MTBLS9872 | MetaboLights
Project description:ObjectiveInsulin suppresses adipose tissue lipolysis after a meal, playing a key role in metabolic homeostasis. This is mediated via the kinase Akt and its substrate phosphodiesterase 3B (PDE3B). Once phosphorylated and activated, PDE3B hydrolyses cAMP leading to the inactivation of cAMP-dependent protein kinase (PKA) and suppression of lipolysis. However, several gaps have emerged in this model. Here we investigated the role of the PDE3B-interacting protein, α/β-hydrolase ABHD15 in this process.MethodsLipolysis, glucose uptake, and signaling were assessed in ABHD15 knock down and knock out adipocytes and fat explants in response to insulin and/or β-adrenergic receptor agonist. Glucose and fatty acid metabolism were determined in wild type and ABHD15-/- littermate mice.ResultsDeletion of ABHD15 in adipocytes resulted in a significant defect in insulin-mediated suppression of lipolysis with no effect on insulin-mediated glucose uptake. ABHD15 played a role in suppressing PKA signaling as phosphorylation of the PKA substrate Perilipin-1 remained elevated in response to insulin upon ABHD15 deletion. ABHD15-/- mice had normal glucose metabolism but defective fatty acid metabolism: plasma fatty acids were elevated upon fasting and in response to insulin, and this was accompanied by elevated liver triglycerides upon β-adrenergic receptor activation. This is likely due to hyperactive lipolysis as evident by the larger triglyceride depletion in brown adipose tissue in these mice. Finally, ABHD15 protein levels were reduced in adipocytes from mice fed a Western diet, further implicating this protein in metabolic homeostasis.ConclusionsCollectively, ABHD15 regulates adipocyte lipolysis and liver lipid accumulation, providing novel therapeutic opportunities for modulating lipid homeostasis in disease.
| S-EPMC6601125 | biostudies-literature
Project description:Adipocyte lipolysis controls systemic energy levels and metabolic homeostasis. Lipolysis is regulated by post-translational modifications of key lipolytic enzymes. However, less is known about the transcriptional mechanisms that regulate lipolysis. Here, we identify the transcriptional factor interferon regulatory factor-2 binding protein 2 (IRF2BP2) as a repressor of adipocyte lipolysis. Deletion of IRF2BP2 in primary human adipocytes increases lipolysis without affecting glucose uptake, whereas IRF2BP2 overexpression decreases lipolysis. RNA-seq and ChIP-seq analyses reveal that IRF2BP2 directly represses several lipolysis-related genes, including LIPE (HSL, hormone sensitive lipase), which encodes the rate-limiting enzyme in lipolysis. Adipocyte-selective deletion of Irf2bp2 in mice increases Lipe expression and free fatty acid levels, resulting in elevated adipose tissue inflammation and glucose intolerance. Altogether, these findings demonstrate that IRF2BP2 restrains adipocyte lipolysis and opens new avenues to target lipolysis for the treatment of metabolic disease.
2024-11-14 | GSE281494 | GEO
Project description:Adipocyte lipolysis controls systemic energy levels and metabolic homeostasis. Lipolysis is regulated by post-translational modifications of key lipolytic enzymes. However, less is known about the transcriptional mechanisms that regulate lipolysis. Here, we identify the transcriptional factor interferon regulatory factor-2 binding protein 2 (IRF2BP2) as a repressor of adipocyte lipolysis. Deletion of IRF2BP2 in primary human adipocytes increases lipolysis without affecting glucose uptake, whereas IRF2BP2 overexpression decreases lipolysis. RNA-seq and ChIP-seq analyses reveal that IRF2BP2 directly represses several lipolysis-related genes, including LIPE (HSL, hormone sensitive lipase), which encodes the rate-limiting enzyme in lipolysis. Adipocyte-selective deletion of Irf2bp2 in mice increases Lipe expression and free fatty acid levels, resulting in elevated adipose tissue inflammation and glucose intolerance. Altogether, these findings demonstrate that IRF2BP2 restrains adipocyte lipolysis and opens new avenues to target lipolysis for the treatment of metabolic disease.
2024-11-14 | GSE281495 | GEO
Project description:Adipocyte lipolysis controls systemic energy levels and metabolic homeostasis. Lipolysis is regulated by post-translational modifications of key lipolytic enzymes. However, less is known about the transcriptional mechanisms that regulate lipolysis. Here, we identify the transcriptional factor interferon regulatory factor-2 binding protein 2 (IRF2BP2) as a repressor of adipocyte lipolysis. Deletion of IRF2BP2 in primary human adipocytes increases lipolysis without affecting glucose uptake, whereas IRF2BP2 overexpression decreases lipolysis. RNA-seq and ChIP-seq analyses reveal that IRF2BP2 directly represses several lipolysis-related genes, including LIPE (HSL, hormone sensitive lipase), which encodes the rate-limiting enzyme in lipolysis. Adipocyte-selective deletion of Irf2bp2 in mice increases Lipe expression and free fatty acid levels, resulting in elevated adipose tissue inflammation and glucose intolerance. Altogether, these findings demonstrate that IRF2BP2 restrains adipocyte lipolysis and opens new avenues to target lipolysis for the treatment of metabolic disease.
2024-11-14 | GSE281493 | GEO