Total RNA transcriptomic profiling of mouse thoracic and abdominal perivascular adipose tissue of mice with an adipocyte-specific deletion of PRDM16 and flox control mice.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE297494 | GEO | 2026/01/23
REPOSITORIES: GEO
Similar Datasets
Project description:Thoracic and abdominal perivascular adipose tissue (tPVAt and aPVAT) is in direct contact with the outer layer of the aorta. While tPVAT exhibits a thermogenic phenotype, aPVAT is mostly comprised of white adipocytes with a few scattered thermogenic adipocytes. To investigate the relevance of this change in adipocyte identity along the aorta, we used mice with an adipocyte-specific deletion of Prdm16 resulting in loss of thermogenic and gain of white adipocyte-like features and compare gene expression signature in these mice.
2026-01-23 | GSE297495 | GEO
Project description:Hypertension, atherosclerosis, and aneurysms alter thoracic aorta structure. Aortic lesions found in these diseases show a unique anatomical distribution. For instance, calcifications and atherosclerotic lesions tend to occur more frequently in the posterior wall of the aorta compared to other regions. The role that the outer layer of the aorta, its perivascular adipose tissue (PVAT), plays in the pathogenesis of these lesions is unknown. The descending thoracic aorta's PVAT is distributed in three strips of tissue: one strip is located anterior to the aorta (AP), while the other two are positioned laterally to the vessel and are adjacent to the thoracic vertebrae (LP). Genetic tracing indicates LP's adipocytes descend from sm22a+ and Myf5+ progenitors while the anterior are from sm22a+ only. The implications of this ontology and aortic PVAT distribution on the development of adipocytes are unknown. We hypothesize that the anatomical location of adipocyte progenitors influences their adipogenic potential. PVAT from LP and AP was collected from male SD rats at 10 wks of age (n=7) to harvest progenitors by outgrowth expansion. Progenitors were differentiated for 4 d in adipogenic media. Adipogenesis was evaluated by lipid droplet and triglyceride quantification using the IncuCyte Live-Cell® system. RNA from progenitors and 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 differences in adipogenic activity and extracellular matrix secretion between the LP and AP PVAT of the aorta. These differences may explain the anatomical location of aortic lesions associated with hypertension, atherosclerosis, and aneurysms.
2023-10-11 | GSE244664 | GEO
Project description:Brown adipose tissue can expend large amounts of energy and thus increasing its amount or activity is a promising therapeutic approach to combat metabolic disease. In humans, major deposits of brown fat cells are found intimately associated with large blood vessels, corresponding to perivascular adipose tissue (PVAT). However, the cellular origins of PVAT are poorly understood. We applied single cell transcriptomic analyses, ex vivo adipogenesis assays, and genetic fate mapping to determine the identity of perivascular adipocyte progenitors. In mice, we found that thoracic PVAT develops from a fibroblastic lineage, consisting of progenitor cells (Pdgfra+; Ly6a+; Pparg-) and preadipocytes (Pdgfra+; Ly6a+; Pparg+). Progenitor and preadipocyte cells in PVAT shared transcriptional similarity with analogous cell types in white adipose tissue, pointing towards a conserved hierarchical structure of adipose lineage cells. Interestingly, the aortic adventitia of adult animals contained a novel population of adipogenic smooth muscle cells (SMCs) (Myh11+; Pdgfra-; Pparg+) that contributed to perivascular adipocyte formation. Similarly, human PVAT contained presumptive fibroblastic and SMC-like adipocyte progenitors, as revealed by single nucleus RNAseq. Taken together, these studies define distinct populations of progenitor cells for thermogenic PVAT, providing a foundation for developing strategies to augment brown fat activity.
2021-04-01 | GSE166355 | GEO
Project description:Energy-storing white adipocytes maintain their identity by suppressing the gene program defining energy-burning thermogenic brown/beige adipocytes. Here, we reveal that the protein-protein interaction between the transcriptional co-regulator ZFP423 and brown/beige cell determination factor, EBF2, is essential for restraining the thermogenic phenotype of white adipose tissue (WAT). Disruption of the ZFP423-EBF2 protein interaction through CRISPR-Cas9 gene editing triggers widespread “browning” of WAT in adult mice. Mechanistically, adipocyte Zfp423 deficiency induces an EBF2 NuRD-to-BAF co-regulator switch and a shift in PPARgamma occupancy to thermogenic genes. This shift in PPARgamma occupancy increases the anti-diabetic efficacy of the PPARgamma agonist rosiglitazone in obesity while diminishing the unwanted weight-gaining effect of the drug. These data indicate that ZFP423 controls EBF2 co-activator recruitment and PPARgamma occupancy to determine the thermogenic plasticity of adipocytes and raise the concept of targeting transcriptional brakes in adipocyte gene expression as a therapeutic strategy to induce thermogenic adipocyte biogenesis in obesity.
2022-05-01 | GSE175654 | GEO
Project description:Energy-storing white adipocytes maintain their identity by suppressing the gene program defining energy-burning thermogenic brown/beige adipocytes. Here, we reveal that the protein-protein interaction between the transcriptional co-regulator ZFP423 and brown/beige cell determination factor, EBF2, is essential for restraining the thermogenic phenotype of white adipose tissue (WAT). Disruption of the ZFP423-EBF2 protein interaction through CRISPR-Cas9 gene editing triggers widespread “browning” of WAT in adult mice. Mechanistically, adipocyte Zfp423 deficiency induces an EBF2 NuRD-to-BAF co-regulator switch and a shift in PPARgamma occupancy to thermogenic genes. This shift in PPARgamma occupancy increases the anti-diabetic efficacy of the PPARgamma agonist rosiglitazone in obesity while diminishing the unwanted weight-gaining effect of the drug. These data indicate that ZFP423 controls EBF2 co-activator recruitment and PPARgamma occupancy to determine the thermogenic plasticity of adipocytes and raise the concept of targeting transcriptional brakes in adipocyte gene expression as a therapeutic strategy to induce thermogenic adipocyte biogenesis in obesity.
2022-05-01 | GSE175653 | GEO
Project description:Brown adipose tissue (BAT) is a central thermogenic organ that enhances energy expenditure (EE) and cardiometabolic health. However, regulators that specifically increase the number of thermogenic adipocytes are still an unmet need. Here, we show by phosphoproteomics that cAMP activates distinct signaling pathways in brown progenitors, with the cAMP-EPAC1 axis enhancing proliferation and differentiation of thermogenic but not white adipocytes. Further analysis revealed that a specific subpopulation of preadipocytes that are PDGFRα-positive express EPAC1. In vivo, pharmacological activation of EPAC1 enhances BAT growth and browning of white fat, leading to increased EE and reduced diet-induced adiposity. In contrast, mice lacking EPAC1 in PDGFRα-positive preadipocytes show the opposite phenotype. Importantly, EPAC1 activation enhances proliferation and differentiation of human brown adipocytes and human brown fat organoids. Interestingly, a coding variant in EPAC1 that positively correlates with BMI abolishes norepinephrine-induced proliferation of brown adipocytes. Thus, EPAC1 might be an attractive target to enhance thermogenic adipocyte number and EE to combat metabolic diseases.
2023-11-11 | PXD046709 | Pride
Project description:We previously established the transcription factor Zfp423 is critical for maintaining white adipocyte identity through suppression of the thermogenic gene program. The loss of Zfp423 in mature adipocytes triggers the rapid conversion of energy-storing white adipocytes into thermogenic beige adipocytes in subcutaneous WAT. In contrast to subcutaneous WAT, visceral WAT is relatively resistant to browning. However, visceral adipocytes lacing Zfp423 are capable of inducing the thermogenic gene program upon β-3 adrenergic stimulus. Here, we generated mice lacking Zfp423 in visceral adipose by breeding transgenic mice expressing Cre recombinase under the control of the Wilms Tumor 1 locus (Wt1-Cre) to animals carrying the floxed Zfp423 alleles (Zfp423loxP/loxP) (“Vis-KO” mice). Inactivation of Zfp423 in visceral WAT gives rise to thermogenic adipocytes that share properties of subcutaneous beige adipocytes and classic brown adipocytes.
2017-04-25 | GSE98132 | GEO
Project description:Despite recent advances in the characterization of the mouse adipocyte epigenome, epigenetic characterization of adipocytes in vivo has been limited, particularly across different adipose depots and of more than two epigenetic modifications. In this study, by using the state-of-the art method CUT&Tag and NuTRAP mice to generate paired single mouse datasets we conducted an integrative multimodal analysis of five histone marks – H3K4me3, H3K27me3, H3K4me1, H3K27ac and H3K9me3 – in beige, brown, and white adipocytes from three distinct mouse adipose tissue depots. Our analysis revealed that enhancers distinguished adipocytes by their tissue of origin, with H3K4me1 deposition differentiating between beige and brown adipocytes. Furthermore, diphtheria toxin-mediated ablation of beige adipocytes showed that white adipocytes in inguinal adipose tissue and beige adipocytes did not use a distinct enhancer set and both poised thermogenic genes for expression. In contrast, adipocytes from epididymal adipose tissue actively repressed thermogenic master regulators and exhibited a distinct enhancer profile compared to white adipocytes from inguinal tissue. These paired multimodal data comprise an extensive resource for the further exploration of the mouse adipocyte epigenome which may enable discovery of regulatory elements governing adipocyte identity and gene regulation.
2025-06-30 | GSE262213 | GEO
Project description:Adipocytes are critical regulators of metabolism and energy balance. While white adipocyte dysfunction is a hallmark of obesity-associated disorders, the activation of thermogenic brown and beige adipocytes is linked to improved cardiometabolic health. As adipocytes dynamically adapt to environmental cues by functionally switching between white and thermogenic phenotypes, a molecular understanding of this adipocyte plasticity could help improving energy balance and weight loss. Here, we show that the long non-coding RNA (lncRNA) Apoptosis associated transcript in bladder cancer (AATBC) is a human-specific regulator of adipocyte plasticity. Searching for new human lncRNAs implicated in adipocyte biology we compared transcriptional profiles of human adipose tissues and cultured adipocytes and discovered that AATBC was enriched in thermogenic conditions. Using primary human adipocytes and immortalized human adipocytes we found that gain-of-function of AATBC enhanced the thermogenic phenotype whereas loss-of-function diminished this effect. The AATBC-mediated increase in mitochondrial respiration was linked to a more fragmented mitochondrial network and vice versa. While we found that AATBC is predominantly located in the nucleus, its effect on global transcription was only marginal. As AATBC is specific to humans, we expressed AATBC in adipose tissue of mice to study its systemic impact, which led to lower plasma leptin levels. Interestingly, this association was also present in human subjects, as AATBC in adipose tissue was inversely correlated with plasma leptin levels, body mass index and other measures of metabolic health. In conclusion, AATBC is a novel obesity-linked regulator of adipocyte plasticity and mitochondrial function in humans.
2023-08-29 | GSE239671 | GEO
Project description:Adipocytes are critical regulators of metabolism and energy balance. While white adipocyte dysfunction is a hallmark of obesity-associated disorders, the activation of thermogenic brown and beige adipocytes is linked to improved cardiometabolic health. As adipocytes dynamically adapt to environmental cues by functionally switching between white and thermogenic phenotypes, a molecular understanding of this adipocyte plasticity could help improving energy balance and weight loss. Here, we show that the long non-coding RNA (lncRNA) Apoptosis associated transcript in bladder cancer (AATBC) is a human-specific regulator of adipocyte plasticity. Searching for new human lncRNAs implicated in adipocyte biology we compared transcriptional profiles of human adipose tissues and cultured adipocytes and discovered that AATBC was enriched in thermogenic conditions. Using primary human adipocytes and immortalized human adipocytes we found that gain-of-function of AATBC enhanced the thermogenic phenotype whereas loss-of-function diminished this effect. The AATBC-mediated increase in mitochondrial respiration was linked to a more fragmented mitochondrial network and vice versa. While we found that AATBC is predominantly located in the nucleus, its effect on global transcription was only marginal. As AATBC is specific to humans, we expressed AATBC in adipose tissue of mice to study its systemic impact, which led to lower plasma leptin levels. Interestingly, this association was also present in human subjects, as AATBC in adipose tissue was inversely correlated with plasma leptin levels, body mass index and other measures of metabolic health. In conclusion, AATBC is a novel obesity-linked regulator of adipocyte plasticity and mitochondrial function in humans.
2023-08-29 | GSE236966 | GEO