A PPARγ-lncRNA axis modulates thermoneutral remodeling of white adipose tissue [snRNA-seq]
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ABSTRACT:
PROVIDER: PRJNA894499 | ENA |
REPOSITORIES: ENA
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Project description:Interplay between parenchymal energy-storing white adipose cells and thermogenic beige adipocytes contributes to obesity and insulin resistance. Irrespective of cellular origin or specialized niche, adipocytes require the activity of the nuclear receptor peroxisome proliferator activated receptor gamma (PPARγ) for proper function. Exposure to cold or adrenergic signaling enriches thermogenic cells though multiple pathways that act synergistically with PPARγ, however, the molecular mechanisms by which PPARγ licenses white adipose tissue (WAT) to preferentially adopt a thermogenic or white adipose fate in response to dietary cues or thermoneutral conditions are not fully elucidated. Here, we show that a PPARγ-long noncoding RNA (lncRNA) axis integrates canonical and noncanonical thermogenesis to restrain white adipose tissue heat dissipation during thermoneutrality and diet-induced obesity (DIO). Pharmacologic inhibition or genetic deletion of the lncRNA Lexis, enhances UCP-1 dependent and independent thermogenesis. Adipose tissue specific deletion of Lexis counteracted diet-induced obesity, improved insulin sensitivity, and enhanced energy expenditure. Single-nuclei transcriptomics revealed that Lexis regulates a distinct population of thermogenic adipocytes. We systematically map Lexis motif preferences and show that it regulates the thermogenic program through the activity of the metabolic GWAS gene and WNT modulator TCF7L2. Collectively, our studies uncover a new mode of crosstalk between PPARγ and WNT signaling that preserves white adipose tissue plasticity.
2023-09-27 | GSE216608 | GEO
Project description:Interplay between parenchymal energy-storing white adipose cells and thermogenic beige adipocytes contributes to obesity and insulin resistance. Irrespective of cellular origin or specialized niche, adipocytes require the activity of the nuclear receptor peroxisome proliferator activated receptor gamma (PPARγ) for proper function. Exposure to cold or adrenergic signaling enriches thermogenic cells though multiple pathways that act synergistically with PPARγ, however, the molecular mechanisms by which PPARγ licenses white adipose tissue (WAT) to preferentially adopt a thermogenic or white adipose fate in response to dietary cues or thermoneutral conditions are not fully elucidated. Here, we show that a PPARγ-long noncoding RNA (lncRNA) axis integrates canonical and noncanonical thermogenesis to restrain white adipose tissue heat dissipation during thermoneutrality and diet-induced obesity (DIO). Pharmacologic inhibition or genetic deletion of the lncRNA Lexis, enhances UCP-1 dependent and independent thermogenesis. Adipose tissue specific deletion of Lexis counteracted diet-induced obesity, improved insulin sensitivity, and enhanced energy expenditure. Single-nuclei transcriptomics revealed that Lexis regulates a distinct population of thermogenic adipocytes. We systematically map Lexis motif preferences and show that it regulates the thermogenic program through the activity of the metabolic GWAS gene and WNT modulator TCF7L2. Collectively, our studies uncover a new mode of crosstalk between PPARγ and WNT signaling that preserves white adipose tissue plasticity.
2023-09-27 | GSE216272 | GEO
Project description:A PPARγ-lncRNA axis modulates thermoneutral remodeling of white adipose tissue
| PRJNA892905 | ENA
Project description:Interplay between parenchymal energy-storing white adipose cells and thermogenic beige adipocytes contributes to obesity and insulin resistance. Irrespective of cellular origin or specialized niche, adipocytes require the activity of the nuclear receptor peroxisome proliferator activated receptor gamma (PPARγ) for proper function. Exposure to cold or adrenergic signaling enriches thermogenic cells though multiple pathways that act synergistically with PPARγ, however, the molecular mechanisms by which PPARγ licenses white adipose tissue (WAT) to preferentially adopt a thermogenic or white adipose fate in response to dietary cues or thermoneutral conditions are not fully elucidated. Here, we show that a PPARγ-long noncoding RNA (lncRNA) axis integrates canonical and noncanonical thermogenesis to restrain white adipose tissue heat dissipation during thermoneutrality and diet-induced obesity (DIO). Pharmacologic inhibition or genetic deletion of the lncRNA Lexis, enhances UCP-1 dependent and independent thermogenesis. Adipose tissue specific deletion of Lexis counteracted diet-induced obesity, improved insulin sensitivity, and enhanced energy expenditure. Single-nuclei transcriptomics revealed that Lexis regulates a distinct population of thermogenic adipocytes. We systematically map Lexis motif preferences and show that it regulates the thermogenic program through the activity of the metabolic GWAS gene and WNT modulator TCF7L2. Collectively, our studies uncover a new mode of crosstalk between PPARγ and WNT signaling that preserves white adipose tissue plasticity.
2023-09-27 | GSE215870 | GEO
Project description:A PPARγ-lncRNA axis modulatesthermoneutral remodeling of white adipose tissue
| PRJNA891073 | ENA
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:Thermoneutral housing regulates intestinal tissue tolerance
| PRJNA665457 | ENA
Project description:Purpose: To identify the impact of thermoneutral housing as opposed to standard housing on gene expression profiles in the mouse peripheral blood mononuclear cells (PBMCs), focusing on proinflammatory immune responses and high-fat diet induced non-alcoholic fatty liver disease pathogenesis. Methods: Expression profiles from PBMCs collected from C57Bl6 mice fed chow or high-fat diet for 8 weeks, following 2 weeks at either standard or thermoneutral housing conditions. Sequencing was performed in duplicate, the Illumina HiSeq 2500. Transcripts that passed quality filters were analyzed at the gene level, using Strand NGS for accurate alignment and quantification. Results: We mapped approximately 20million reads per sample to the mm10 genome using annotations produced by Ensembl, which represented 36186 transcripts. Approximately 14000 genes exhibited reasonable expression in at least one experimental condition. The primary focus was the effect of housing temperature while holding diet consistent (i.e. thermoneutral vs standard, both on high-rat diet), where ~2700 genes exhibited differential regulation. Conclusions: We present the transcriptomic profile of PBMCs from mice fed chow of high-fat diets, following either standard or thermoneutral housing. We obseve an augmented proinflammatory immune response.
2017-02-12 | GSE80976 | GEO
Project description:Purpose: To investigate the involvement of mTORC1 as a mediator of the actions of the PPARγ ligand rosiglitazone in subcutaneous inguinal white adipose tissue transcriptome; Methods: Mice bearing regulatory associated protein of mTOR (Raptor) deletion and therefore mTORC1 deficiency exclusively in adipocytes (adiponectin Cre recombinase) and littermate controls were fed a high-fat diet supplemented or not with the PPARγ agonist rosiglitazone (30 mg/kg/day) for 8 weeks and evaluated for inguinal white adipose tissue transcriptome (Rnaseq); Results: 3,2425 genes had their correspondent mRNA levels altered by either adipocyte Raptor deficiency or rosiglitazone administration or their combination. Among those, 408 genes modulated by rosiglitazone required mTORC1. Conclusion: PPARγ and mTORC1 are essential partners in the regulation of a cluster of genes in inguinal white adipose tissue.
2022-02-01 | GSE166988 | GEO
Project description:The peroxisome proliferator-activated receptor γ (PPARγ) is the master regulator of adipocyte differentiation, and mutations that interfere with PPARγ function cause lipodystrophy. Structural studies indicate that PPARγ domains engage in several intra- and inter-moleuclar interactions; however, how these interactions modulate the ability of PPARγ to activate target genes in a cellular context is currently poorly understood. Here we analysed the transcriptional potential of R212Q and E379K two previously uncharacterised lipodystrophy-associated PPARγ mutants that are located in distinct PPARγ domains but are both predicted to affect intermolecular interactions. Using a combination of biochemical and genome-wide approaches we show that these mutations impair binding to an overlapping subset of enhancers that are less accessible and specifically require PPARγ for chromatin remodeling. Based on these findings we propose a model in which recruitment of PPARγ to chromatin is determined by several intermolecular interfaces. Furthermore, our data exemplify that relatively subtle molecular defects in transcription factors are sufficient to significantly affect enhancer binding and thereby transcriptional output.
2022-09-08 | PXD036589 | Pride