ArticleNature metabolism2024
Obesity causes mitochondrial fragmentation and dysfunction in white adipocytes due to RalA activation.
Article in Nature metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
What it found
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Who cites it
100 citing papers in PubMed, 124 citations in OpenAlex.
- Targeting mitochondrial quality control in diabetic kidney disease: emerging therapeutic opportunities.Renal failure · 2026Review
- Metabolic drivers of MASLD and MASH: from hormonal imbalance to fibrosis.Diabetologia · 2026Review
- Cardiovascular-kidney-metabolic syndrome as a mitochondrial systems disorder.Nature reviews. Nephrology · 2026Review
- Adipose Tissue Expandability as a Link Between Nutrition and Obesity-Related Metabolic Risk: Insights from Bariatric Surgery.Nutrients · 2026Review
- UA-30 ameliorates motor deficits through RalA-mediated mitophagy in ALS mice.The Journal of clinical investigation · 2026Article
- Natural Small Molecules Targeting Mitochondrial Quality Control for the Treatment of Metabolic Diseases: Mechanisms, Novel Formulations, and Translational Perspectives.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Stable Isotope-Resolved Metabolomics in Elucidating Mitochondrial Metabolic Reprogramming and Therapeutic Targets.Biomedical chromatography : BMC · 2026Review
- Adipose-cartilage communication via EV-Mito-mtDNA signaling promotes osteoarthritis progression.Science advances · 2026Article
- IRF1 in Adipocytes Is Associated with Insulin Signaling and Mitochondrial Homeostasis in Diet-Induced Obesity.International journal of molecular sciences · 2026Article
- E4BP4 safeguards brown fat mitochondria from obesity-induced fragmentation via ceramide repression.EMBO reports · 2026Article
- Article
- Mitochondrial quality control in health and disease: mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Metainflammation, Mitochondrial Dysfunction, and Organokine Crosstalk: A Central Axis Linking Metabolic Syndrome to Cardiovascular Diseases.International journal of molecular sciences · 2026Review
- The effect of weight-loss surgery in patients with obesity on adipose tissue mesenchymal stem cells versus circulating endothelial progenitor cells.International journal of obesity (2005) · 2026Article
- Article
- Association of the C-reactive protein-triglyceride-glucose (CTI) index and its central obesity-modified derivatives with incident cardiometabolic multimorbidity: results from two prospective cohorts in China and England.Cardiovascular diabetology · 2026Article
- Alternative organelle targeting of OPA1 mediates fatty acid release from lipid droplets.bioRxiv : the preprint server for biology · 2026Article
- The Role of Oral Pathobionts' Outer Membrane Vesicles in Cancer Pathology and Therapeutic Development.Cells · 2026Review
- Mitochondrial Dysfunction at the Intersection of CKM Syndrome: Molecular Mechanisms and Path-to-Target Therapies.International journal of molecular sciences · 2026Review
- Targeting the Ras-Ral Signaling Axis in Type 2 Diabetes Mellitus: A Dual-Modulation Approach to Correcting Insulin Resistance and β-Cell Dysfunction.Pharmaceuticals (Basel, Switzerland) · 2026Review
40 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 9 institutions in 4 countries.
Funding
Abstract
Mitochondrial dysfunction is a characteristic trait of human and rodent obesity, insulin resistance and fatty liver disease. Here we show that high-fat diet (HFD) feeding causes mitochondrial fragmentation in inguinal white adipocytes from male mice, leading to reduced oxidative capacity by a process dependent on the small GTPase RalA. RalA expression and activity are increased in white adipocytes after HFD. Targeted deletion of RalA in white adipocytes prevents fragmentation of mitochondria and diminishes HFD-induced weight gain by increasing fatty acid oxidation. Mechanistically, RalA increases fission in adipocytes by reversing the inhibitory Ser637 phosphorylation of the fission protein Drp1, leading to more mitochondrial fragmentation. Adipose tissue expression of the human homolog of Drp1, DNM1L, is positively correlated with obesity and insulin resistance. Thus, chronic activation of RalA plays a key role in repressing energy expenditure in obese adipose tissue by shifting the balance of mitochondrial dynamics toward excessive fission, contributing to weight gain and metabolic dysfunction.
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Registered trials
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 Socratic graph.