ArticleMolecular metabolism2022
Proteasome dysfunction disrupts adipogenesis and induces inflammation via ATF3.
Article in Molecular metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- Persistent effects of pre-differentiation manganese exposure on adipogenesis and metabolic function in differentiated 3T3-L1 adipocyte cells.Journal of hazardous materials advances · 2026Article
- Epigenome-wide analysis in West Africans identifies DNA methylation markers for circulating adiponectin.EBioMedicine · 2026Article
- Molecular mechanisms in rare proteasomopathies.EULAR rheumatology open · 2026Review
- Unravelling distinct patterns of metagenomic surveillance and respiratory microbiota between two P1 genotypes ofEmerging microbes & infections · 2025Article
- Expression and DNA methylation of 20S proteasome subunits as prognostic and resistance markers in cancer.Molecular oncology · 2025Article
- Human iPSC-derived salivary gland organoids model diabetic salivary gland dysfunction.bioRxiv : the preprint server for biology · 2025Article
- A novel indirubin- 3-monoxime derivative I3MV- 8b exhibits remarkable cytotoxicity against multiple myeloma by targeting TRIM28.Biomarker research · 2025Article
- Emerging concepts and treatments in autoinflammatory interferonopathies and monogenic systemic lupus erythematosus.Nature reviews. Rheumatology · 2025Review
- Associations Between Obstructive Sleep Apnea and Metabolic Dysfunction-Associated Fatty Liver Disease: Insights from Comprehensive Mendelian Randomization and Gene Expression Analysis.Nature and science of sleep · 2025Article
- Integrating Single-Cell RNA-Seq and ATAC-Seq Analysis Reveals Uterine Cell Heterogeneity and Regulatory Networks Linked to Pimpled Eggs in Chickens.International journal of molecular sciences · 2024Article
- Integration of ATAC-Seq and RNA-Seq Reveals VDR-SELENBP1 Axis Promotes Adipogenesis of Porcine Intramuscular Preadipocytes.International journal of molecular sciences · 2024Article
- IF1 is a cold-regulated switch of ATP synthase hydrolytic activity to support thermogenesis in brown fat.The EMBO journal · 2024Article
- Understanding neurodevelopmental proteasomopathies as new rare disease entities: A review of current concepts, molecular biomarkers, and perspectives.Genes & diseases · 2024Review
- Systems genetics analysis of human body fat distribution genes identifies adipocyte processes.Life science alliance · 2024Article
- Review
- The multifaceted roles of activating transcription factor 3 (ATF3) in inflammatory responses - Potential target to regulate neuroinflammation in acute brain injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Review
- The role of proteasome activators PA28αβ and PA200 in brown adipocyte differentiation and function.Frontiers in endocrinology · 2023Article
- Cloning, distribution, and effects of growth regulation of MC3R and MC4R in red crucian carp (Frontiers in endocrinology · 2023Article
- ATF3 in atherosclerosis: a controversial transcription factor.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Identification of the Transcription Factor ATF3 as a Direct and Indirect Regulator of the LDLR.Metabolites · 2022Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveRegulation of proteasomal activity is an essential component of cellular proteostasis and function. This is evident in patients with mutations in proteasome subunits and associated regulators, who suffer from proteasome-associated autoinflammatory syndromes (PRAAS). These patients display lipodystrophy and fevers, which may be partly related to adipocyte malfunction and abnormal thermogenesis in adipose tissue. However, the cell-intrinsic pathways that could underlie these symptoms are unclear. Here, we investigate the impact of two proteasome subunits implicated in PRAAS, Psmb4 and Psmb8, on differentiation, function and proteostasis of brown adipocytes.
methodsIn immortalized mouse brown pre-adipocytes, levels of Psmb4, Psmb8, and downstream effectors genes were downregulated through reverse transfection with siRNA. Adipocytes were differentiated and analyzed with various assays of adipogenesis, lipogenesis, lipolysis, inflammation, and respiration.
resultsLoss of Psmb4, but not Psmb8, disrupted proteostasis and adipogenesis. Proteasome function was reduced upon Psmb4 loss, but partly recovered by the activation of Nuclear factor, erythroid-2, like-1 (Nfe2l1). In addition, cells displayed higher levels of surrogate inflammation and stress markers, including Activating transcription factor-3 (Atf3). Simultaneous silencing of Psmb4 and Atf3 lowered inflammation and restored adipogenesis.
conclusionsOur study shows that Psmb4 is required for adipocyte development and function in cultured adipocytes. These results imply that in humans with PSMB4 mutations, PRAAS-associated lipodystrophy is partly caused by disturbed adipogenesis. While we uncover a role for Nfe2l1 in the maintenance of proteostasis under these conditions, Atf3 is a key effector of inflammation and blocking adipogenesis. In conclusion, our work highlights how proteasome dysfunction is sensed and mitigated by the integrated stress response in adipocytes with potential relevance for PRAAS patients and beyond.
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