Brd4 modulates diet-induced obesity via PPARγ-dependent Gdf3 expression in adipose tissue macrophages

Hu, Xiangming; Dong, Xingchen; Guo, Li; Chen, Yanheng; Chen, Jinjing; He, Xian; Sun, Hao; Kim, Dong-Hyun; Kemper, Jongsook Kim; Chen, Linfeng

doi:10.1172/jci.insight.143379

Cited by 16 publications

(12 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…KDM7A [61], LMNA (lamin A/C) [62], PFKFB3 [63], NEU1 [64], DUSP22 [65], ADORA2B [66], CRTC2 [67], GRN (granulin precursor) [68], CTSD (cathepsin D) [69], IGFBP4 [70], SMYD2 [71], OSM (oncostatin M) [72], INVS (inversin) [73], ANKFY1 [74], SEMA4D [75], PPM1A [76], IFNG (interferon gamma) [77], CTBP1 [78], ATP6 [79], COX2 [80], RPS19 [81], COX1 [82] and TLK1 [83] are potential biomarkers for the detection and prognosis of renal diseases. A previous study reported that LXN (latexin) [84], LMNA (lamin A/C) [85], PFKFB3 [86], NEU1 [87], TBK1 [88], GRN (granulin precursor) [89], CTSD (cathepsin D) [90], ACADS (acyl-CoA dehydrogenase short chain) [91], IRF7 [92], S1PR1 [93], ZAP70 [94], IDH1 [95], IL15 [96], PIK3R1 [97], OSM (oncostatin M) [98], SOCS3 [99], USP21 [100], CEP19 [101], KDM2A [102], TP53 [103], BRD2 [104], ATP6 [105], BRD4 [106], COX2 [107], RPS6 [108], ND2 [109], CYTB (cytochrome b) [110] and COX1 [111] are altered expressed in obesity. Altered expression of BCL3 [112], TRAF2 [113], NEU1 [114], SNAP29 [115], AGPAT2 [116], LPCAT3 [117], ADORA2B [118], CTSD (cathepsin D) [119], ACADS (acyl-CoA dehydrogenase short chain) [120], ACAD9 [121], E4F1 [122], IRF7 [123], TAF1 [124], S1PR1 [125], RASSF1 [126], ELAC2 [127], RNF146 [128], COX15 [129], SMYD2 [130], IDH1 [131], MTO1 [132], IL15 [133], PIK3R1 [13...…”

Section: Discussionmentioning

confidence: 99%

“…Enrichment analysis of GO and REACTOME pathway was carried out to explore the interaction between DEGs. Pathways include metabolism [ [89], CTSD (cathepsin D) [90], ACADS (acyl-CoA dehydrogenase short chain) [91], IRF7 [92], S1PR1 [93], ZAP70 [94], IDH1 [95], IL15 [96], PIK3R1 [97], OSM (oncostatin M) [98], SOCS3 [99], USP21 [100], CEP19 [101], KDM2A [102], TP53 [103], BRD2 [104], ATP6 [105], BRD4 [106], COX2 [107], RPS6 [108], ND2 [109], CYTB (cytochrome b) [110] and COX1 [111] are altered expressed in obesity. Altered expression of BCL3 [112], TRAF2 [113], NEU1 [114], SNAP29 [115], AGPAT2 [116], LPCAT3 [117], ADORA2B [118], CTSD (cathepsin D) [119], ACADS (acyl-CoA dehydrogenase short chain) [120], ACAD9 [121], E4F1 [122], IRF7 [123], TAF1 [124], S1PR1 [125], RASSF1 [126], ELAC2 [127], RNF146 [128], COX15 [129], SMYD2 [130], IDH1 [131], MTO1 [132], IL15 [133], PIK3R1 [134], ASB1 …”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Bioinformatics Analysis of next generation sequencing data for Risk Prediction in Patients with Type 1 diabetes mellitus

Vastrad¹,

Vastrad²

2022

Preprint

View full text Add to dashboard Cite

Type 1 diabetes mellitus (T1DM) comprise the most common forms of autoimmune disease. The aim of this investigation was to apply a bioinformatics approach to reveal related pathways or genes involved in the development of T1DM. The next generation sequencing (NGS) dataset GSE182870 was downloaded from the gene expression omnibus (GEO) database. Differentially expressed gene (DEG) analysis was performed using DESeq2. The g:Profiler was utilized to analyze the functional enrichment, gene ontology (GO) and REACTOME pathway of the differentially expressed genes. Protein-protein interaction (PPI) network, modules, miRNA-hub gene regulatory network, and TF-hub gene regulatory network were conducted via comprehensive target prediction and network analyses. Finally, hub genes were validated by using receiver operating characteristic curve analysis. A total of 860 DEGs were screened out from NGS dataset, among which 477 genes were up regulated and 383 genes were down regulated. GO enrichment analysis indicated that up regulated genes were mainly involved in cellular metabolic process, intracellular anatomical structure and catalytic activity, and the down regulated genes were significantly enriched in cellular nitrogen compound biosynthetic process, protein containing complex and heterocyclic compound binding. REACTOME pathway enrichment analysis showed that the up regulated genes were mainly enriched in metabolism of carbohydrates and the down regulated genes were significantly enriched in metabolism of RNA. A PPI network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network were constructed, and hub genes (MAPK14, RHOC, MAD2L1, TAF1, TRAF2, HSP90AA1, TP53, HSP90AB1, UBA52 and RACK1) were identified. This study provides further insights into the underlying pathogenesis of T1DM.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis of next generation sequencing data for Risk Prediction in Patients with Type 1 diabetes mellitus

Vastrad¹,

Vastrad²

2022

Preprint

View full text Add to dashboard Cite

show abstract

“…The copyright holder for this preprint this version posted November 7, 2022. ; https://doi.org/10.1101/2022.11.07.515236 doi: bioRxiv preprint Similarly, GDF3 secreted by macrophages infiltrating skeletal muscle after injury can promote skeletal muscle repair and regeneration (24)(25)(26)(27)(28)(29). The molecular mechanism of how GDF3 affects insulin resistance, muscle glucose uptake, muscle regeneration, and myoblast fusion are still unclear.…”

Section: Discussionmentioning

confidence: 99%

GDF3 simultaneously antagonizes BMP signaling and activates TGFβ receptor signaling

Ramachandran

Kotikalapudi

Maridas

et al. 2022

Preprint

View full text Add to dashboard Cite

Growth differentiation factor 3 (Gdf3) is a relatively understudied member of the Tgfβ superfamily. GDF3 is highly expressed in stem cell populations and restricts cellular differentiation. Gdf3 expression levels decrease after development only to rise in states of obesity and inflammation. However, the function of GDF3 in adult mammalian biology is contentious. To understand the impact of GDF3 on cellular signaling we explored the cellular responses to either recombinant GDF3 or an inducible genetically-encoded Gdf3 in C2C12 myoblasts. In addition, we employ fluorescent reporters to simultaneously assay both BMP receptor signaling through a SMAD1/5/8 DNA-binding BMP-responsive element and TGFβ receptor signaling through a SMAD3 DNA-binding element. We find that GDF3 is capable of dose-dependent inhibition of multiple BMP proteins including BMP2, BMP7, BMP9, BMP10, and BMP15. We also find that GDF3 produces a bona fide activin-like ligand signaling through the TGFBR2 receptor. Expression profiling with RNA-seq reveals that BMP2-regulated genes are attenuated by the addition of GDF3. Together these results clarify the dual biological roles of Gdf3 in cultured myoblasts.

show abstract

“…In this study, using HFHC diet-induced mouse models that encompass 2 time periods, we compared the WAT transcriptome and identified 118 cytokines selectively dysregulated in the WAT of NASH mice. Some of these cytokines have been shown to regulate adipogenesis (such as Wnt10b and Angptl2), adipose inflammation (such as Gdf3 and Cyr61), and fat mass and energy expenditure (such as Fgf10 and Vegfb) in adipose tissues (66)(67)(68)(69)(70)(71). Whether they play a role in the development of NASH through direct or indirect mechanisms remains poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Sparcl1 promotes nonalcoholic steatohepatitis progression in mice through upregulation of CCL2

Liu¹,

Xiang²,

Ji³

et al. 2021

Journal of Clinical Investigation

View full text Add to dashboard Cite

Brd4 modulates diet-induced obesity via PPARγ-dependent Gdf3 expression in adipose tissue macrophages

Cited by 16 publications

References 52 publications

Bioinformatics Analysis of next generation sequencing data for Risk Prediction in Patients with Type 1 diabetes mellitus

Bioinformatics Analysis of next generation sequencing data for Risk Prediction in Patients with Type 1 diabetes mellitus

GDF3 simultaneously antagonizes BMP signaling and activates TGFβ receptor signaling

Sparcl1 promotes nonalcoholic steatohepatitis progression in mice through upregulation of CCL2

Contact Info

Product

Resources

About