Obesity drives depot-specific vascular remodeling in white adipose tissue
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ABSTRACT:
PROVIDER: PRJEB83704 | ENA |
REPOSITORIES: ENA
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Project description:Obesity-driven pathological expansion of white adipose tissue (WAT) is a key driver of endothelial dysfunction. Contrary to this paradigm, early vascular alterations associated with over nutrition also exacerbate AT dysfunction. To dissect this complex cause and consequence relationship, here we perform a single-cell transcriptomics screen to generate a detailed landscape of endothelial heterogeneity and vascular alterations in murine model of obesity. Given the differences in ontogeny and function of distinct WAT depots, we demarcate key differences in subcutaneous and visceral WAT vasculature. In addition to descriptive taxonomy, we perform in-depth validation and characterization of our in silico data. We identify a sWAT specific fenestrated endothelial cell subtype, which is drastically reduced in obese conditions. This reduction was associated with a decrease in VEGFA expressing perivascular cells. The novel endothelial subtypes provide a basis for future research and new directions for therapeutic interventions.
2023-05-26 | E-MTAB-12855 | biostudies-arrayexpress
Project description:Single nucleus RNA sequencing (snRNA-seq), an alternative to single cell RNA sequencing (scRNA-seq), encounters technical challenges in obtaining high-quality nuclei and RNA, persistently hindering its applications. Here, we present a robust technique for isolating nuclei across various tissue types, remarkably enhancing snRNA-seq data quality. Employing this approach, we comprehensively characterize the depot-dependent cellular dynamics of various cell types underlying adipose tissue remodeling during obesity. By integrating nuclear RNA-seq data from adipocyte nuclei of varying sizes, we identify distinct adipocyte subpopulations categorized by size and functionality. Specifically, we characterize dysfunctional hypertrophic adipocytes prevalent in visceral adipose tissues during obesity, exhibiting cellular stress, inflammation and impaired metabolic gene expression. Obesity-induced changes in gene expression profiles of adipocyte subpopulations reveal their distinct contributions to adipose tissue pathophysiology. Our study establishes a robust snRNA-seq method, providing novel insights into the mechanisms orchestrating adipose tissue remodeling during obesity, with broader applicability across diverse biological systems.
2024-04-01 | GSE261417 | GEO
Project description:Robust single nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity
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Project description:Although inflammation plays critical roles in the development of atherosclerosis, its regulatory mechanisms remain incompletely understood. Perivascular adipose tissue (PVAT) has been reported to undergo inflammatory changes in response to vascular injury. Here, we showed that vascular injury induced the beiging (brown adipose tissue-like phenotype change) of PVAT, which fine-tunes inflammatory response and thus vascular remodeling as a protective mechanism. In a mouse model of endovascular injury, macrophages accumulated in PVAT, causing beiging phenotype change. Inhibition of PVAT beiging by genetically silencing PRDM16, a key regulator to beiging, exacerbated inflammation and vascular remodeling following injury. Conversely, activation of PVAT beiging attenuated inflammation and pathological vascular remodeling. Single-cell RNA sequencing revealed that beige adipocytes abundantly expressed neuregulin 4 (Nrg4) which critically regulated alternative macrophage activation. Importantly, significant beiging was observed in the diseased aortic PVAT in patients with acute aortic dissection. Taken together, vascular injury induced the beiging of adjacent PVAT with macrophage accumulation, where NRG4 secreted from the beige PVAT facilitated alternative activation of macrophages, leading to the resolution of vascular inflammation. Our study demonstrated the pivotal roles of PVAT in vascular inflammation and remodeling and will open a new avenue for treating atherosclerosis.
2022-06-21 | GSE206399 | GEO
Project description:Adipose tissue plays a pivotal role in energy homeostasis and metabolic regulation. However, in obesity, the remarkable adaptability of adipose tissue becomes impaired. The underlying mechanisms behind this limited adaptability remain poorly understood. In this study, we investigate a novel layer of regulation involving translation in the adipose stromal vascular fraction, examining its response to obesity and acute PPARγ agonist treatment with rosiglitazone. Using single-cell RNA sequencing, we establish a transcriptional profile atlas of cellular remodeling from obese to lean-like states in inguinal and epididymal adipose tissue following rosiglitazone treatment. Notably, both stromal fractions exhibit a downregulation of inflammation-related transcripts and an upregulation of lipid-related metabolism and ribosomal transcripts. Adipocyte progenitor and preadipocyte populations display enhanced ex-vivo differentiation potential and upregulation in ribosome and peptide chain elongation pathways. This ribosomal remodeling is directly driven by PPARγ binding to gene promoters of ribosomal factors. Furthermore, we have characterized the translatome in the epididymal stromal fraction, highlighting a buffering response and fat-exclusive preferential translation after rosiglitazone treatment. Enhanced translation efficiency in rosiglitazone-elicited polysomes promotes the translation of transcripts containing G-rich sequences in their 5’ untranslated regions. Our findings shed light and provide a resource on how rosiglitazone remodels the adipose stromal vascular fraction, both dependent and independent of PPARγ. Importantly, we uncover translatome remodeling as a major new mechanism for maintaining translation homeostasis and preserving adipose tissue health in obesity.
2024-10-02 | GSE267192 | GEO
Project description:Robust snRNA-seq protocol revealing mouse white adipose tissue remodeling during obesity
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Project description:Adipose tissue plays a pivotal role in energy homeostasis and metabolic regulation. However, in obesity, the remarkable adaptability of adipose tissue becomes impaired. The underlying mechanisms behind this limited adaptability remain poorly understood. In this study, we investigate a novel layer of regulation involving translation in the adipose stromal vascular fraction, examining its response to obesity and acute PPAR? agonist treatment with rosiglitazone. Using single-cell RNA sequencing, we establish a transcriptional profile atlas of cellular remodeling from obese to lean-like states in inguinal and epididymal adipose tissue following rosiglitazone treatment. Notably, both stromal fractions exhibit a downregulation of inflammation-related transcripts and an upregulation of lipid-related metabolism and ribosomal transcripts. Adipocyte progenitor and preadipocyte populations display enhanced ex-vivo differentiation potential and upregulation in ribosome and peptide chain elongation pathways. This ribosomal remodeling is directly driven by PPAR? binding to gene promoters of ribosomal factors. Furthermore, we have characterized the translatome in the epididymal stromal fraction, highlighting a buffering response and fat-exclusive preferential translation after rosiglitazone treatment. Enhanced translation efficiency in rosiglitazone-elicited polysomes promotes the translation of transcripts containing G-rich sequences in their 5? untranslated regions. Our findings shed light and provide a resource on how rosiglitazone remodels the adipose stromal vascular fraction, both dependent and independent of PPAR?. Importantly, we uncover translatome remodeling as a major new mechanism for maintaining translation homeostasis and preserving adipose tissue health in obesity. PLEASE NOTE: the raw fastq files for sample inputVeh3 were corrupted and, therefore, no longer retrievable. However, the processed data file (inputVeh3_quant.sf) for this sample is still usable.
2024-10-02 | GSE268057 | GEO
Project description:Using our robust snRNA-seq protocol effectively enhancing nucleus integrity and RNA quality, we comprehensivly characterize the dynamics of cell populations within mouse epididymal and inguinal adipose tissues during obesity.
2024-08-01 | GSE241987 | GEO
Project description:Hypoxia can induce vasoconstriction followed by vascular remodeling including hypertrophy and hyperplasia of pulmonary vascular smooth muscle and proliferation of endothelial cells. The goal of this project is to elucidate the genes involved in vascular remodeling following pulmonary hypertension. Total RNA was isolated from lungs of normoxic and hypoxic treated animals. Keywords: other
2003-07-16 | GSE482 | GEO
Project description:Case story. A patient with massive infiltration of the visceral adipose tissue depot by BAT in a patient with a catecholamine secreting paraganglioma. BAT tissue was identified by protein expression of UCP1 (western blotting and immunostaining) The goal of the study is to identify patterns of gene expression in BAT containing visceral fat compared to the patient's own subcutanous fat which did not express BAT. For comparison a pool of mRNA isolated from visceral fat from obese subjects was used. Patient Case, Gene expression array from a biopsy from the patient's visceral fat and a biopsy from the subcutaneous fat compared to one array of mRNA from the visceral depot pooled from a group of obese subjects
2014-08-12 | E-GEOD-49795 | biostudies-arrayexpress