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Next generation sequencing analysis of microRNAs in brown preadipocytes and in vitro differentiated mature brown fat cells

ABSTRACT: We performed a genome-wide deep sequencing analysis of the microRNAs abundant in mesenchymal stem cells (MSCs) derived from murine brown adipose tissue and in in vitro differentiated mature brown adipocytes. Several microRNAs were identified as differentially regulated when comparing datasets from MSCs vs. mature fat cells. These microRNAs may have an implication in the regulation of adipogenesis as well as thermogenesis in brown adipose tissue (BAT).

ORGANISM(S): Mus musculus

PROVIDER: GSE45499 | GEO | 2013/05/28

SECONDARY ACCESSION(S): PRJNA194535

REPOSITORIES: GEO

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Next generation sequencing analysis of microRNAs in brown preadipocytes and in vitro differentiated mature brown fat cells

Project description:We performed a genome-wide deep sequencing analysis of the microRNAs abundant in mesenchymal stem cells (MSCs) derived from murine brown adipose tissue and in in vitro differentiated mature brown adipocytes. Several microRNAs were identified as differentially regulated when comparing datasets from MSCs vs. mature fat cells. These microRNAs may have an implication in the regulation of adipogenesis as well as thermogenesis in brown adipose tissue (BAT). Examination of BAT-derived MSCs (BAT-MSC; 1 sample) and in vitro differentiated mature brown fat cells (BAT-DIFF; 1 sample) vertis biotechnologie AG, D-85354 Freising, Germany (library construction and sequencing)

2013-05-28 | E-GEOD-45499 | biostudies-arrayexpress

Taf7l Modulates Brown Adipose Tissue Formation

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

Absence of MCJ/DnaJC15 promotes brown adipose tissue thermogenesis

Project description:Obesity poses a global health challenge, demanding a deeper understanding of adipose tissue (AT) and its mitochondria. This study describes the role of the mitochondrial protein Methylation-controlled J protein (MCJ/DnaJC15) in orchestrating brown adipose tissue (BAT) thermogenesis. Here we show how MCJ expression decreases during obesity, as evident in human and mouse adipose tissue samples. MCJKO mice, even without UCP1, a fundamental thermogenic protein, exhibit elevated BAT thermogenesis. Electron microscopy unveils changes in mitochondrial morphology resembling BAT activation. Proteomic analysis confirms these findings and suggests involvement of the eIF2α mediated stress response. The pivotal role of eIF2α is scrutinized by in vivo CRISPR deletion of eIF2α in MCJKO mice, abrogating thermogenesis. These findings uncover the importance of MCJ as a regulator of BAT thermogenesis, presenting it as a promising target for obesity therapy.

2024-11-13 | PXD057026 | Pride

Sympathetic inputs regulate adaptive thermogenesis in brown adipose tissue through cAMP-Salt inducible kinase axis

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

Single-nucleus RNA sequencing of mouse brown adipose tissue

Project description:Here, we performed single nucleus RNA sequencing on mouse brown adipose tissues to investigate the gene expression patterns relative to BAT thermogenesis mechanism using denervation model.

2022-07-03 | GSE207096 | GEO

Lrpprc deficiency in brown adipocytes diminishes cold-induced thermogenesis but improves systemic metabolism

Project description:Insufficient mitochondrial quantity in brown adipose tissue (BAT) causes defective thermogenesis and positive energy balance, which is coupled with the development of obesity. Whether disturbance of mitochondrial quality affects BAT function remains unknown. Here, we describe that the brown adipocyte-specific Leucine-rich PPR motif-containing protein knockout mice (LrpprcBKO) exhibited mitochondrial electron transport chain (ETC) proteome imbalance and a complete loss of the -adrenergic-stimulated thermogenesis at room temperature (RT), due to specific reduction of mtDNA-encoded genes. However, the LrpprcBKO mice were lean at normal chow and were protected against high-fat-diet-induced metabolic abnormalities, such as obesity, insulin resistance, adipose inflammation, hepatic steatosis, and hypertriglyceridemia. The beige adipocytes in inguinal white adipose tissue were expanded in LrpprcBKO mice at RT, but not at thermoneutrality. However, BAT thermogenic defects and metabolic benefits were present in LrpprcBKO mice regardless of ambient temperatures. Collectively, our results reveal that a thermogenesis-incapable BAT with mitochondrial ETC proteome imbalance can improve systemic metabolism, suggesting BAT’s contributions to thermoregulation and systemic metabolism can be uncoupled.

2021-10-07 | PXD008798 | Pride

RNA-seq of age-associated transcriptome changes in brown adipose tissue

Project description:Brown adipose tissue (BAT) plays a central role in energy homeostasis through non-shivering thermogenesis. Besides, recent human studies using 18FDG-PET/CT imaging demonstrated that BAT acts as a significant metabolic-sink for glucose. Notably, these functions in BAT decrease with age: however what regulates this process remains poorly understood. To this end, we employed RNA-seq to identify the transcriptional changes in BAT of young and old mice.

2019-07-20 | E-MTAB-7445 | biostudies-arrayexpress

Exosomal Proteins and Brown Fat Activation

Project description:Brown adipose tissue (BAT) is a promising weapon to combat obesity and metabolic disease. BAT is thermogenic and consumes substantial amounts of glucose and fatty acids as fuel for thermogenesis and energy expenditure. To study BAT function in large human longitudinal cohorts, safe and precise detection methodologies are needed. Although regarded a gold standard, the foray of PET-CT into BAT research and clinical applications is limited by its high ionizing radiation doses. Here, we show that brown adipocytes release exosomes in blood plasma which can be utilized to assess BAT activity. In this study, we investigated circulating protein biomarkers that can accurately and reliably reflect BAT activation triggered by cold exposure, capsinoids ingestion and thyroid hormone excess in humans.

2022-06-09 | PXD023909 | Pride

Transcriptomics of FGF6-stimulated mouse brown preadipocytes

Project description:Uncoupling protein-1 (UCP1) plays a central role in energy dissipation in brown adipose tissue (BAT). Using high-throughput library screening of secreted peptides, we identified two fibroblast growth factors (FGF), FGF6 and FGF9, as novel and potent inducers of UCP1 expression in adipocytes and preadipocytes. Here we show the transcriptome of FGF6-stimulated mouse brown preadipocytes.

2020-02-07 | GSE144061 | GEO

Proteome imbalance of mitochondrial electron transport chain in brown adipocytes leads to metabolic benefits

Project description:Adaptive thermogenesis of brown adipose tissue (BAT) is critical for thermoregulation and contributes to total energy expenditure. However, whether BAT has non-thermogenic functions is largely unknown. Here, we describe that mice with a BAT-specific Liver kinase b1 deletion (Lkb1BKO mice) exhibited impaired mitochondrial respiration and thermogenesis in BAT, but reduced adiposity and liver triglyceride accumulation under high-fat-diet feeding at room temperature. Importantly, these metabolic benefits were also present in Lkb1BKO mice at thermoneutrality, where BAT thermogenesis was not required. Mechanistically, decreased mRNA levels of mtDNA-encoded electron transport chain (ETC) subunits and ETC proteome imbalance led to impaired mitochondrial respiration in BAT of Lkb1BKO mice. Furthermore, reducing mtDNA gene expression directly in BAT by removing mitochondrial transcription factor A (Tfam) in BAT also showed ETC proteome imbalance and the tradeoff between BAT thermogenesis and systemic metabolism at both room temperature and thermoneutrality. Collectively, our data demonstrates that ETC proteome imbalance in BAT regulates systemic metabolism independently of BAT thermogenic capacity.

2018-07-12 | PXD008599 | Pride

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