A PPARγ-lncRNA axis modulates thermoneutral remodeling of white adipose tissue
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA892905 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22002040_1.fastq.gz | Fastqsanger.gz | |||
| SRR22002040_2.fastq.gz | Fastqsanger.gz | |||
| SRR22002041_1.fastq.gz | Fastqsanger.gz | |||
| SRR22002041_2.fastq.gz | Fastqsanger.gz | |||
| SRR22002042_1.fastq.gz | Fastqsanger.gz |
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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 | GSE216272 | 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 | GSE216608 | GEO
Project description:A PPARγ-lncRNA axis modulates thermoneutral remodeling of white adipose tissue [snRNA-seq]
| PRJNA894499 | 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: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:We identify fibroblast growth factor 1 (FGF1) as a critical transducer in adipose tissue remodeling and link its regulation to peroxisome proliferator activated-receptor γ (PPARγ), the adipocyte master regulator and target of the thiazolidinedione (TZD) class of insulin sensitizing drugs. We show that FGF1 is highly induced in adipose tissue in response to high-fat diet (HFD) and that mice lacking FGF1 develop an aggressive diabetic phenotype coupled to aberrant adipose expansion when challenged with HFD. Mechanistically, we show that transcription of FGF1 is directly regulated by an adipocyte-selective proximal PPAR response element, and that this PPARγ-FGF1 axis is evolutionarily conserved in mammals. This work describes the first phenotype of the FGF1 knockout mouse and establishes FGF1 as a new member of the NR-FGF axis critical for maintaining metabolic homeostasis and insulin sensitization.
2012-04-23 | GSE31692 | GEO
Project description:Brown adipose tissue (BAT) can disperse stored energy as heat. Promoting BAT-like features in white adipose (WAT) is an attractive, if elusive, therapeutic approach to staunch the current obesity epidemic. Here we report that gain of function of the NAD-dependent deacetylase SirT1 or loss of function of its endogenous inhibitor Deleted in breast cancer-1 (Dbc1) promote "browning" of WAT by deacetylating peroxisome proliferator-activated receptor (Ppar)-γ on Lys268 and Lys293. SirT1-dependent deacetylation of Lys268 and Lys293 is required to recruit the BAT program coactivator Prdm16 to Pparγ, leading to selective induction of BAT genes and repression of visceral WAT genes associated with insulin resistance. An acetylation-defective Pparγ mutant induces a brown phenotype in white adipocytes, whereas an acetylated mimetic fails to induce "brown" genes but retains the ability to activate "white" genes. We propose that SirT1-dependent Pparγ deacetylation is a form of selective Pparγ modulation of potential therapeutic import.
| S-EPMC3413172 | biostudies-literature
Project description:Macrophage-mediated inflammatory response has been implicated in the pathogenesis of obesity and insulin resistance. Brd4 has emerged as a key regulator in the innate immune response. However, the role of Brd4 in obesity-associated inflammation and insulin resistance remains uncharacterized. Here, we demonstrated that myeloid-lineage specific Brd4 knockout (Brd4-CKO) mice were protected from high-fat-diet (HFD)-induced obesity with less fat accumulation, higher energy expenditure, and increased lipolysis in adipose tissue. Brd4-CKO mice also displayed reduced local and systemic inflammation with improved insulin sensitivity upon HFD. RNA-sequencing of adipose tissue macrophages (ATMs) from HFD-fed wide-type and Brd4-CKO mice revealed that expression of antilipolytic factor Gdf3 was significantly decreased in ATMs of Brd4-CKO mice. We also found that Brd4 bound to the promoter and enhancers of Gdf3 to facilitate PPARγ-dependent Gdf3 expression in macrophages. Furthermore, Brd4-mediated expression of Gdf3 acted as a paracrine signal targeting adipocytes to suppress the expression of lipases and the associated lipolysis in cultured cells and mice. Controlling the expression of Gdf3 in ATMs could be one of the mechanisms by which Brd4 modulates lipid metabolism and diet-induced obesity. This study suggests that Brd4 could be a potential therapeutic target for obesity and insulin resistance.
2021-03-24 | GSE169475 | GEO
Project description:Adipose tissue plays a pivotal role in energy homeostasis and metabolic regulation. However, in obesity, the remarkable adaptability of adipose tissue becomes impaired. The underlying mechanisms behind this limited adaptability remain poorly understood. In this study, we investigate a novel layer of regulation involving translation in the adipose stromal vascular fraction, examining its response to obesity and acute PPARγ agonist treatment with rosiglitazone. Using single-cell RNA sequencing, we establish a transcriptional profile atlas of cellular remodeling from obese to lean-like states in inguinal and epididymal adipose tissue following rosiglitazone treatment. Notably, both stromal fractions exhibit a downregulation of inflammation-related transcripts and an upregulation of lipid-related metabolism and ribosomal transcripts. Adipocyte progenitor and preadipocyte populations display enhanced ex-vivo differentiation potential and upregulation in ribosome and peptide chain elongation pathways. This ribosomal remodeling is directly driven by PPARγ binding to gene promoters of ribosomal factors. Furthermore, we have characterized the translatome in the epididymal stromal fraction, highlighting a buffering response and fat-exclusive preferential translation after rosiglitazone treatment. Enhanced translation efficiency in rosiglitazone-elicited polysomes promotes the translation of transcripts containing G-rich sequences in their 5’ untranslated regions. Our findings shed light and provide a resource on how rosiglitazone remodels the adipose stromal vascular fraction, both dependent and independent of PPARγ. Importantly, we uncover translatome remodeling as a major new mechanism for maintaining translation homeostasis and preserving adipose tissue health in obesity.
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