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LncRNAs expression profiling in adipose tissues and during brown adipocyte differentiation

ABSTRACT: Brown and beige fats generate heat via uncoupled respiration to defend against cold, mechanistically, through the action of a network of transcription factors and cofactors. Here we globally profiled long noncoding RNAs (lncRNAs) gene expression during thermogenic adipocyte formation and identified Brown fat lncRNA 1 (Blnc1) as a novel nuclear lncRNA that promotes brown and beige adipocyte differentiation and function by forming a feedforward regulatory loop with EBF2 to drive adipogenesis toward thermogenic phenotype.

ORGANISM(S): Mus musculus

PROVIDER: GSE57643 | GEO | 2015/02/28

SECONDARY ACCESSION(S): PRJNA247393

REPOSITORIES: GEO

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LncRNAs expression profiling in adipose tissues and during brown adipocyte differentiation

Project description:Brown and beige fats generate heat via uncoupled respiration to defend against cold, mechanistically, through the action of a network of transcription factors and cofactors. Here we globally profiled long noncoding RNAs (lncRNAs) gene expression during thermogenic adipocyte formation and identified Brown fat lncRNA 1 (Blnc1) as a novel nuclear lncRNA that promotes brown and beige adipocyte differentiation and function by forming a feedforward regulatory loop with EBF2 to drive adipogenesis toward thermogenic phenotype. LncRNAs expression were measured in BAT and WAT from mice injected saline/CL and during brown adipocyte differentiation with two replicates using Arraystar Mouse LncRNA microarray V2.0

2015-02-28 | E-GEOD-57643 | biostudies-arrayexpress

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Project description:Blnc1 is a novel nuclear lncRNA that promotes brown and beige adipocyte differentiation and function. Blnc1 forms a ribonucleoprotein complex with transcription factor EBF2 to stimulate the thermogenic gene program. Further, Blnc1 itself is a target of EBF2, thereby forming a feedforward regulatory loop to drive adipogenesis toward thermogenic phenotype. We used microarrays to elucidate the role of Blnc1 on brown adipocyte differentiation and the induction of the thermogenic gene program. Brown adipocytes expressing vector or brown fat lncRNA 1 (blnc1) were differentiated for 6 days and harvested for RNA isolation and microarray using Affymetrix Mouse MG-430 PM Strip arrays. Two replicated samples were included in this study.

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ZFP423 Controls EBF2 Co-activator Recruitment and PPARgamma Occupancy to Determine the Thermogenic Plasticity of Adipocytes_ChIP-seq

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.

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Project description:Long noncoding RNAs (lncRNAs) are emerging as powerful regulators of adipocyte differentiation and gene expression. However, their physiological role in adipose tissue biology and systemic energy metabolism has not been established. Here we show that adipose tissue expression of Blnc1, a conserved lncRNA regulator of thermogenic genes, is highly induced in obese mice. Fat-specific inactivation of Blnc1 impairs cold-induced thermogenesis and browning, exacerbates obesity-associated brown fat whitening, and worsens adipose tissue inflammation and fibrosis, leading to more severe insulin resistance and hepatic steatosis. On the contrary, transgenic expression of Blnc1 in adipose tissue elicits the opposite and beneficial metabolic effects, supporting a critical role of Blnc1 in driving adipose adaptation during obesity. Mechanistically, Blnc1 cell-autonomously attenuates proinflammatory cytokine signaling and promotes fuel storage in adipocytes through its protein partner Zbtb7b. This study illustrates a surprisingly pleiotropic and dominant role of lncRNA in driving adaptive adipose tissue remodeling and preserving metabolic health.

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Transcriptional control of thermogenesis by early B cell proteins [RNA-seq]

Project description:Early B Cell Factor 2 (EBF2) is required for brown adipose tissue basal thermogenic gene expression; however, it was unknown whether chronic cold exposure normalized the expression of thermogenic genes in Ebf2 mutant mice. We examined the transcriptome of Ebf2 WT and mutant brown adipose tissue in mice housed at room temperature or one week of cold exposure.

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