ArticleNature metabolism2021
The mitochondrial protein Opa1 promotes adipocyte browning that is dependent on urea cycle metabolites.
Article in Nature metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.
- Mitochondria-associated regulation in adipose tissues and potential reagents for obesity intervention.Frontiers in endocrinology · 2023Pooled it
- Article
- Mitochondrial quality control in health and disease: mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Alternative organelle targeting of OPA1 mediates fatty acid release from lipid droplets.bioRxiv : the preprint server for biology · 2026Article
- Adipose Tissue Engineering Biomaterials: Smart Scaffolds, Vascularization, and Clinical Frontiers.Biomolecules · 2026Review
- Systemic cachexia and muscle-bone crosstalk drive depression-related joint remodeling and pain.International journal of surgery (London, England) · 2026Article
- Latest Advances in Obesity Treatment by Regulating Adipocyte Thermogenesis.PPAR research · 2026Review
- Thermogenesis is limited by cellular competence.Frontiers in cell and developmental biology · 2026Article
- Mitochondria-Localized Nestin Protects Mesenchymal Stem Cells from Senescence by Maintaining Cristae Structure and Function.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The multifaceted regulation of white adipose tissue browning and their therapeutic potential.Journal of physiology and biochemistry · 2025Review
- Mitochondrial dysfunction in adipocyte differentiation: implications for obesity and metabolic syndrome intervention.Acta biochimica et biophysica Sinica · 2025Article
- Small-molecule OPA1 inhibitors reverse mitochondrial adaptations to overcome therapy resistance in acute myeloid leukemia.Science advances · 2025Article
- 2-hydroxyglutarate mediates whitening of brown adipocytes coupled to nuclear softening upon mitochondrial dysfunction.Nature metabolism · 2025Article
- Interaction Between Rumen Microbiota and Epithelial Mitochondrial Dynamics in Tibetan Sheep: Elucidating the Mechanism of Rumen Epithelial Energy Metabolism.Biotech (Basel (Switzerland)) · 2025Article
- MOB1 deletion in murine mature adipocytes ameliorates obesity and diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Rare ginsenosides transformed from stems and leaves ofJournal of ginseng research · 2025Article
- Ablation of FAM210A in Brown Adipocytes of Mice Exacerbates High-Fat Diet-Induced Metabolic Dysfunction.Diabetes · 2025Article
- Leptin drives glucose metabolism to promote cardiac protection via OPA1-mediated HDAC5 translocation and Glut4 transcription.Functional & integrative genomics · 2025Article
- Mitochondrial dynamics govern whole-body regeneration through stem cell pluripotency and mitonuclear balance.Nature communications · 2024Article
- Mitochondrial mechanotransduction through MIEF1 coordinates the nuclear response to forces.Nature cell biology · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
White to brown/beige adipocytes conversion is a possible therapeutic strategy to tackle the current obesity epidemics. While mitochondria are key for energy dissipation in brown fat, it is unknown if they can drive adipocyte browning. Here, we show that the mitochondrial cristae biogenesis protein optic atrophy 1 (Opa1) facilitates cell-autonomous adipocyte browning. In two cohorts of patients with obesity, including weight discordant monozygotic twin pairs, adipose tissue OPA1 levels are reduced. In the mouse, Opa1 overexpression favours white adipose tissue expandability as well as browning, ultimately improving glucose tolerance and insulin sensitivity. Transcriptomics and metabolomics analyses identify the Jumanji family chromatin remodelling protein Kdm3a and urea cycle metabolites, including fumarate, as effectors of Opa1-dependent browning. Mechanistically, the higher cyclic adenosine monophosphate (cAMP) levels in Opa1 pre-adipocytes activate cAMP-responsive element binding protein (CREB), which transcribes urea cycle enzymes. Flux analyses in pre-adipocytes indicate that Opa1-dependent fumarate accumulation depends on the urea cycle. Conversely, adipocyte-specific Opa1 deletion curtails urea cycle and beige differentiation of pre-adipocytes, and is rescued by fumarate supplementation. Thus, the urea cycle links the mitochondrial dynamics protein Opa1 to white adipocyte browning.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.