HuR-dependent gene expression in brown adipose tissue
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE154820 | GEO | 2020/07/22
REPOSITORIES: GEO
Similar Datasets
Project description:HuR-dependent gene expression in brown adipose tissue
| PRJNA647811 | ENA
Project description:Human antigen R (HuR) is a member of the Hu family of RNA-binding proteins and is involved in many physiological processes. To investigate the role of adipose HuR, we generate adipose-specific HuR knockout (HuRAKO) mice. As compared with control mice, HuRAKO mice show obesity when induced with a high-fat diet, along with insulin resistance, glucose intolerance, hypercholesterolemia and increased inflammation in adipose tissue. The obesity of HuRAKO mice is attributed to adipocyte hypertrophy in white adipose tissue due to decreased expression of adipose triglyceride lipase (ATGL), a critical lipase involved in lipolysis. HuR positively regulates ATGL expression by promoting the mRNA stability and translation of ATGL. Consistently, the expression of HuR in adipose tissue is reduced in obese humans, which is associated with reduced ATGL expression. This study suggests that adipose HuR may be a critical regulator of ATGL expression and lipolysis and thereby controls obesity and metabolic syndrome.
2019-04-23 | GSE130147 | GEO
Project description:Brown adipose tissue (BAT) in rabbits undergoes rapid involution, i.e. transforming to white adipose tissue (WAT), similarly to what happens in humans. We aim to profile the transcriptomic changes of total BAT and the stromal vascular fraction (SVF) that contains adipocyte progenitors at the global and single-cell levels.
2021-12-31 | GSE148891 | GEO
Project description:The coexistence of brown adipocytes with low and high thermogenic activity is a fundamental feature of brown adipose tissue (BAT) heterogeneity and plasticity. However, the mechanisms that govern thermogenic adipocyte heterogeneity and its significance in obesity and metabolic disease remain poorly understood. Here we show that in male mice, a population of JunB-enriched (JunB+) adipocytes within the BAT exhibits lower thermogenic capacity compared to high-thermogenic adipocytes. To determine if JunB plays a role in the control of brown adipocyte heterogeneity in thermogenesis, we performed single-nucleus RNA sequencing (snRNA-seq) of BAT from JunB FKO and control mice (3-month-old male mice (5/group)) housed at room temperature. Our study pointing to a potent inhibition by JunB in the conversion from low- to high-thermogenic adipocyte.
2023-10-03 | GSE244239 | GEO
Project description:PGE2/EP3 signaling and m6A modification is required for brown adipocyte differentiation and BAT development, but the underlying mechanisms involved remain to be elucidated. The Arraystar mousen M6a-MRNA&lncRNA Epitranscriptomic microarray analysis was performed on mouse brown preadipocytes with or without EP3 deletion.
2022-04-18 | GSE200924 | GEO
Project description:Aging, chronic high fat diet feeding and housing at thermoneutrality induces brown adipose tissue (BAT) involution, a process characterized by reduction of BAT mass and function with increased lipid droplet size. Syntaxin 4 (STX4) was identified as a healthy longevity gene, in contrast endogenous STX4 protein levels in BAT declined in aged mice resulting in pyroptotic activation of caspase 1/4 signaling pathway. Single nuclei RNA sequencing of aged mice identified a specific brown adipocyte population of UCP1low cells that were Stx4 low and pyroptotic. Similarly, UCP1Stx4KO mice led to age-dependent loss of brown adipose tissue mass concomitant with increased pyroptosis whereas restoring STX4 expression protected against pyroptosis and decline in thermogenic activity. Moreover, STX4 deficiency reduced oxidative phosphorylation, glucose uptake and glycolysis leading to reduced ATP levels, a known signal for pyroptosis. All these data demonstrate a new model of rapid brown adipocyte involution and that physiologic aging and BAT involution results from pyroptotic signaling activation.
2024-02-26 | GSE229999 | GEO
Project description:We report that monocytes contribute to the maintenance of BAT macrophages in a dynamic manner at steady state, and allow tissue remodelling during BAT expansion. Using scRNA-Seq, we explored monocyte and macrophage diversity in BAT at steady state and during BAT expansion.
2021-06-13 | GSE177635 | GEO
Project description:PR (PRD1-BF1-RIZ1 homologous) domain-containing 16 (PRDM16) drives a brown fat differentiation program, but the mechanisms by which PRDM16 activates brown fat-selective genes have been unclear. Through chromatin immunoprecipitation (ChIP) followed by deep sequencing (ChIP-seq) analyses in brown adipose tissue (BAT), we reveal that PRDM16 binding is highly enriched at a broad set of brown fat-selective genes. Importantly, we found that PRDM16 physically binds to MED1, a component of the Mediator complex, and recruits it to superenhancers at brown fat-selective genes. PRDM16 deficiency in BAT reduces MED1 binding at PRDM16 target sites and causes a fundamental change in chromatin architecture at key brown fat-selective genes. Together, these data indicate that PRDM16 controls chromatin architecture and superenhancer activity in BAT.
2015-02-10 | GSE63964 | GEO
Project description:The presence of functional brown adipose tissue in humans is known to be associated with cardiovascular health. Here, we show that adipocyte-specific deletion of the RNA binding protein HuR, which we have previously shown to reduce BAT-mediated thermogenesis, is sufficient to mediate a spontaneous development of cardiac hypertrophy and fibrosis, likely through increased inflammation and extracellular vesicle transport in subcutaneous white adipose tissue. These results may have implications on the mechanisms by which BAT function and adipose tissue homeostasis directly mediates CVD.
2021-07-23 | GSE174193 | GEO
Project description:Tissue resident macrophages provide a systemic innate immune defense network and critically contribute to establishment and maintenance of tissue homeostasis. Here we used constitutive and inducible mutagenesis to delete the nuclear transcription regulator methyl-CpG binding protein 2 (MeCP2) in defined tissue macrophages. Animals lacking the Rett syndrome-associated gene in macrophages did not show signs of neurodevelopmental disorder, but surprisingly displayed altered body composition and spontaneous obesity. This phenotype involved neither hyper-phagia, primary hyper-insulinemia nor inflammation, but rather could be linked to impaired brown adipose tissue (BAT) function. Specifically, mutagenesis of a BAT-resident CX3CR1+ macrophage subpopulation compromised homeostatic, though not acute cold-induced thermogenesis. Mechanistically, steady state BAT malfunction of pre-obese mice harboring mutant macrophages was associated with decreased sympathetic innervation and lower local norepinephrine titers, resulting in reduced adipocyte expression of the thermogenic factors UCP1 and DIO2. Mutant macrophages were found to over-express PlexinA4, which might contribute to the phenotype by repulsion of Sema6A-expressing sympathetic axons. Collectively, we report a previously unappreciated homeostatic role of macrophages in the control of tissue innervation, disruption of which in BAT results in metabolic imbalance.
2017-05-01 | GSE95859 | GEO