Transcriptomics of FGF6-stimulated mouse brown preadipocytes
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE144061 | GEO | 2020/02/07
REPOSITORIES: GEO
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Project description:Brown adipose tissue (BAT) holds therapeutic potential for obesity and metabolic syndrome via increasing energy expenditure. Both inter- and intra-individual differences contribute to heterogeneity in human BAT and potentially to differential thermogenic capacity in human populations. Here, we demonstrated the generation of brown and white preadipocyte clones from human neck fat and characterized their adipogenic differentiation and thermogenic function. Combining a UCP1 reporter system and gene expression profiling, we defined novel sets of gene signatures in human preadipocytes that could predict the thermogenic potential of mature adipocytes. Knocking out the positive UCP1 regulators, PREX1 and EDNRB, in brown preadipocytes by CRISPRs markedly abolished the high level of UCP1 in mature brown adipocytes. Finally, we showed the ability to prospectively isolate adipose progenitors with great thermogenic potential. These data provide new insights into the cellular heterogeneity in human fat and offer clinically relevant gene targets that mark thermogenically competent preadipocytes. Highly adipogenic clonal white and brown cell lines
2015-06-15 | E-GEOD-68544 | biostudies-arrayexpress
Project description:Transcriptomics of FGF6-stimulated mouse brown preadipocytes
| PRJNA602669 | ENA
Project description:Brown adipose tissue (BAT) holds therapeutic potential for obesity and metabolic syndrome via increasing energy expenditure. Both inter- and intra-individual differences contribute to heterogeneity in human BAT and potentially to differential thermogenic capacity in human populations. Here, we demonstrated the generation of brown and white preadipocyte clones from human neck fat and characterized their adipogenic differentiation and thermogenic function. Combining a UCP1 reporter system and gene expression profiling, we defined novel sets of gene signatures in human preadipocytes that could predict the thermogenic potential of mature adipocytes. Knocking out the positive UCP1 regulators, PREX1 and EDNRB, in brown preadipocytes by CRISPRs markedly abolished the high level of UCP1 in mature brown adipocytes. Finally, we showed the ability to prospectively isolate adipose progenitors with great thermogenic potential. These data provide new insights into the cellular heterogeneity in human fat and offer clinically relevant gene targets that mark thermogenically competent preadipocytes.
2015-06-15 | GSE68544 | GEO
Project description:Strategies to increase energy expenditure are an attractive approach to reduce excess fat storage and body weight to improve metabolic health. In mammals, uncoupling protein-1 (UCP1) in brown and beige adipocytes uncouples fatty acid oxidation from ATP generation in mitochondria and promotes energy dissipation as heat. We set out to identify small molecules that enhance UCP1 levels and activity using a high-throughput screen of nearly 12,000 compounds in mouse brown adipocytes. We identified Z16078526 that increases Ucp1 and mitochondrial-related gene expression in mouse brown adipocytes.
2019-12-01 | GSE138264 | GEO
Project description:Various physiological stimuli, such as cold environment, diet, and hormones, trigger brown adipose tissue (BAT) to produce heat through sympathetic nervous system (SNS)- and -adrenergic receptors (ARs). The AR stimulation increases intracellular cAMP levels through heterotrimeric G proteins and adenylate cyclases, but the processes by which cAMP modulates brown adipocyte function are not fully understood. Here we described that specific ablation of cAMP production in brown adipocytes led to reduced lipolysis, mitochondrial biogenesis, uncoupling protein 1 (Ucp1) expression, and consequently defective adaptive thermogenesis. Elevated cAMP signaling by sympathetic activation inhibited Salt-inducible kinase 2 (Sik2) through protein kinase A (PKA)-mediated phosphorylation in brown adipose tissue. Inhibition of SIKs enhanced Ucp1 expression in differentiated brown adipocytes and Sik2 knockout mice exhibited enhanced adaptive thermogenesis at thermoneutrality in an Ucp1-dependent manner. Taken together, our data indicate that suppressing Sik2 by PKA-mediated phosphorylation is a requisite for SNS-induced Ucp1 expression and adaptive thermogenesis in BAT, and targeting Sik2 may present a novel therapeutic strategy to ramp up BAT thermogenic activity in humans.
2018-07-12 | PXD009262 | Pride
Project description:Brown adipose tissue (BAT) plays an essential role in metabolic homeostasis by dissipating energy via thermogenesis through uncoupling protein 1 (Ucp1). Previously, we reported that the TATA-binding protein Associated Factor 7L (Taf7l) is an important regulator of white adipose tissue (WAT) differentiation. Here, we show that Taf7l also serves as a molecular switch between brown fat and muscle lineages in vivo and in vitro. In adipose tissue, Taf7l containing TFIID complexes associate with PPAR to mediate DNA looping between distal enhancers and core promoter elements. Our findings suggest that presence of the tissue-specific Taf7l subunit in TFIID functions to promote long-range chromatin interactions during BAT lineage specification. mRNA-seq expression profiling wild type and Taf7l knockout interscapular brown adipose tissue (BAT)
2014-06-03 | E-GEOD-55797 | biostudies-arrayexpress
Project description:The activation of brown/beige adipose tissue (BAT) metabolism and the induction of uncoupling protein-1 (UCP1) expression are essential for BAT-based strategies to improve metabolic homeostasis. Adrenergic signaling is viewed as a key regulator of thermogenesis and UCP1-expression in BAT, while also operating as a potent contractile stimulator in muscle. The muscle-like gene expression patterns of UCP1+ adipocytes have previously been utilized as tissue specific markers, but have not been attributed with any functional role. Here, we demonstrate that BAT utilizes actomyosin machinery to generate tensional responses following adrenergic stimulation, similar to muscle tissues. We show that activation of actomyosin mechanics are critical for the acute induction of oxidative metabolism and uncoupled respiration in UCP1+ adipocytes. Additionally, actomyosin-mediated elasticity regulates mechanosensitive transcriptional co-activators, YAP/TAZ, that facilitate the thermogenic capacity of adipocytes. These unappreciated signaling and mechanical mechanisms may inform future strategies to promote the expansion and activation of brown/beige adipocytes.
2018-03-01 | GSE109829 | GEO
Project description:Objective: Brown adipose tissue (BAT) is important for thermoregulation in many mammals. Uncoupling protein 1 (UCP1) is the critical regulator of thermogenesis in BAT. Here we aimed to investigate the deacetylation control of BAT and to investigate a possible functional connection between UCP1 and sirtuin 3 (SIRT3), the master mitochondrial deacetylase.
Methods: We carried out physiological, molecular and proteomic analyses of BAT from wild-type and Sirt3KO mice when BAT is activated. Mice were either cold exposed for 2 days or were injected with the β3-adrenergic agonist, CL316,243 (1mg/kg; i.p.). Mutagenesis studies were conducted in a cellular model to assess the impact of acetyaltion lysine sites on UCP1 function. Cardiac punctures were collected for Proteomic analysis of Acylcarnitines. Isolated mitochondria were used for functional analysis of OXPHOS.
Results: Our findings showed that SIRT3 absence in mice resulted in impaired BAT lipid use, whole body thermoregulation, and respiration in BAT mitochondria, without affecting UCP1 expression. Acetylome profiling of BAT mitochondria revealed that SIRT3 regulates acetylation status of many BAT mitochondrial proteins including UCP1 and crucial upstream proteins. Mutagenesis work in cells suggested that UCP1 activity was independent of direct SIRT3-regulated lysine acetylation. However, SIRT3 impacted BAT mitochondrial activities of acylcarnitine metabolism and specific electron transport chain complexes, CI and CII.
2019-04-18 | PXD013056 | Pride
Project description:Obesity has become a global health problem. Brown adipose tissue (BAT), specialized for energy expenditure through thermogenesis, potently counteracts obesity. Recently, BAT is also identified in human adults. We found that Lgr4 homozygous mutant (Lgr4m/m) mice display reduced adiposity and exhibit brown-like adipocytes in their WAT depots with higher expression of uncoupling protein 1 (Ucp1). Furthermore, Lgr4 ablation potentiates brown adipocyte differentiation from stromal vascular fraction (SVF) of epididymal WAT (eWAT) in vitro. We used microarrays to emxamine the gene expression profiles of the brown-like adipocytes differentiated from SVF of wild-type and Lgr4 mutant mice. We identified distinct gene expression profiles of these two groups.
2013-11-07 | GSE47760 | GEO
Project description:Non-shivering thermogenesis in adipocytes is mediated by brown adipose tissue, purportedly through the sole action of uncoupling protein 1 (UCP1). The physiological relevance of UCP1-dependent thermogenesis has primarily been inferred from the attenuation of thermogenic output of mice genetically lacking Ucp1 from birth (germline Ucp1-/-). However, germline Ucp1-/- mice harbor secondary changes within brown adipose tissue beyond UCP1, such as reduced electron transport chain abundance. We show here that these secondary changes also encompass reduced expression of genes regulating fuel liberation, changes that would attenuate the capacity of any thermogenic pathway. Therefore, the quantitative contribution of UCP1-dependent and -independent thermogenesis is not fully understood. To mitigate the potentially confounding ancillary changes to brown adipose tissue of germline Ucp1-/- mice, we constructed mice with inducible adipocyte-selective disruption of Ucp1. We find that, while germline Ucp1-/- mice succumb to cold-induced hypothermia with complete penetrance, most mice with inducible deletion of Ucp1 maintain homeothermy in the cold. However, inducible adipocyte-selective co-deletion of Ucp1 and creatine kinase B (Ckb, an effector of UCP1-independent thermogenesis) exacerbates cold-intolerance, indicative of a negative genetic interaction and thus a parallel thermogenic function. We find no evidence for impairments in insulation or non-shivering thermogenesis in skeletal muscle that would drive this phenotype. Furthermore, following UCP1 deletion or UCP1/CKB co-deletion from mature adipocytes, moderate cold exposure triggers the regeneration of mature adipocytes that coordinately restore UCP1 and CKB to brown adipose tissue, providing further evidence of their parallel thermogenic relationship. Our findings suggest that thermogenic adipocytes utilize non-paralogous protein redundancy – through UCP1 and CKB – to promote cold-induced energy dissipation.
2024-01-10 | PXD047841 | Pride