ArticleeLife2021
OPA1 deletion in brown adipose tissue improves thermoregulation and systemic metabolism via FGF21.
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Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53citing papers in PubMed
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53 citing papers in PubMed, 77 citations in OpenAlex.
- OPA1 controls mitochondrial dysfunction-driven liver fibrosis in MASLD.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial quality control in health and disease: mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Cox10-mediated mitochondrial respiration in brown adipocytes regulates adaptive thermogenesis and systemic metabolism.iScience · 2026Article
- Gdf15 expression in thermogenic adipocytes regulates diet-induced weight gain in a sex-dependent manner.Molecular medicine (Cambridge, Mass.) · 2026Article
- Alternative organelle targeting of OPA1 mediates fatty acid release from lipid droplets.bioRxiv : the preprint server for biology · 2026Article
- GFRAL is required to mediate changes in systemic metabolism in response to mitochondrial stress in brown adipose tissue.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Thermogenesis is limited by cellular competence.Frontiers in cell and developmental biology · 2026Article
- Acute deletion of PLIN5 in brown adipocytes causes mitochondrial dysfunction and cold intolerance.bioRxiv : the preprint server for biology · 2026Article
- Latest Advances in Obesity Treatment by Regulating Adipocyte Thermogenesis.PPAR research · 2026Review
- Sex Differences in Ketogenic Diet Response Reveal Gonadal Hormone Interaction With FGF21 in Mice.Journal of the Endocrine Society · 2025Article
- Mammalian mitohormesis: from mitochondrial stressors to organismal benefits.The EMBO journal · 2025Review
- FGF21 and GDF15 Act Synergistically to Regulate Systemic Metabolic Homeostasis in Mice Lacking OPA1 in Thermogenic Adipocytes.Obesity (Silver Spring, Md.) · 2025Article
- Hypertension Remission After Bariatric Surgery: Metrics, Mechanisms, and Patient Selection.Current cardiology reports · 2025Review
- 2-hydroxyglutarate mediates whitening of brown adipocytes coupled to nuclear softening upon mitochondrial dysfunction.Nature metabolism · 2025Article
- The loss of OPA1 accelerates intervertebral disc degeneration and osteoarthritis in aged mice.Nature communications · 2025Article
- ATF4 Deletion in Brown Adipocytes Attenuates Diet-Induced Insulin Resistance in Male Mice Independently of Weight Gain.Endocrinology · 2025Article
- Ablation of FAM210A in Brown Adipocytes of Mice Exacerbates High-Fat Diet-Induced Metabolic Dysfunction.Diabetes · 2025Article
- Creating Optimal Western Blot Conditions for OPA1 Isoforms in Skeletal Muscle Cells and Tissue.Current protocols · 2025Article
- Research progress on the role of FGF21 in insulin resistance.Frontiers in endocrinology · 2025Review
- Gut microbiota-mitochondrial crosstalk in obesity: novel mechanistic insights and therapeutic strategies with traditional Chinese medicine.Frontiers in pharmacology · 2025Review
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Authors and funding
19 authors at 1 institution in 1 country.
Renata O PereiraFraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States.ORCID 0000-0001-5809-4669
Alex MartiFraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States.
Angela Crystal OlveraFraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States.
Satya Murthy TadinadaFraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States.
Sarah Hartwick BjorkmanFraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States.
Eric Thomas WeatherfordFraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States.
Donald A MorganDepartment of Neuroscience and Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States.
Michael WestphalFraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States.
Pooja H PatelFraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States.ORCID 0000-0002-5345-0158
Ana Karina KirbyFraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States.
Rana HeweziFraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States.
William Bùi TrânFraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States.
Luis Miguel García-PeñaFraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States.ORCID 0000-0001-8718-6490
Rhonda A SouvenirFraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States.ORCID 0000-0002-8880-2483
Monika MittalFraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States.
Christopher M AdamsFraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States.
Kamal RahmouniFraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States.
Matthew J PotthoffFraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States.
E Dale AbelFraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States.ORCID 0000-0001-5290-0738
University of Iowa · US
Funding
Vector Core-Core 2P30DK054759 · NIDDK · UNIVERSITY OF IOWA · PI Alejandro Antonio Pezzulo · 1998 to 2026
$30.5MPROGRAM IN HEMOSTASIS AND THROMBOSIS FOR ACADEMICT32HL007344 · NHLBI · UNIVERSITY OF IOWA · PI Anil Kumar Chauhan, Steven R Lentz · 1985 to 2026
$6.5MInterdisciplinary Training Program in MetabolismT32DK091317 · NIDDK · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI SCOTT A SUMMERS · 2011 to 2026
$4.8MDiabetes Research Training Program Diversity SupplementT32DK112751 · NIDDK · UNIVERSITY OF IOWA · PI Andrew W Norris · 2017 to 2026
$4.8MNovel Signaling Pathways Underlying Skeletal Muscle AtrophyR01AG060637 · NIA · UNIVERSITY OF IOWA · PI ADAMS, CHRISTOPHER M · 2018 to 2022
$2.6MMolecular pathogenesis of skeletal muscle atrophyR01AR071762 · NIAMS · UNIVERSITY OF IOWA · PI ADAMS, CHRISTOPHER M · 2017 to 2021
$2.4MInsulin Inhibition of beta-AR Signaling in the MyocardiumR01HL127764 · NHLBI · UNIVERSITY OF IOWA · PI ABEL, E DALE, XIANG, YANG K · 2015 to 2018
$2.4MThe role of the integrated stress response in brown adipose tissue-mediated metabolic adaptationsR01DK125405 · NIDDK · UNIVERSITY OF IOWA · PI PEREIRA ALAMBERT, RENATA · 2020 to 2024
$1.9MCardiac Dysfunction in the Met Syndrome: Cross-talk between IR and bAR SignalingR01HL112413 · NHLBI · UNIVERSITY OF IOWA · PI ABEL, E DALE, XIANG, YANG K · 2015 to 2018
$1.6MIowa Post-Baccalaureate Research Education in the Biomedical SciencesR25GM116686 · NIGMS · UNIVERSITY OF IOWA · PI DOKUN, AYOTUNDE OLUROPO, WRIGHT, MICHAEL E · 2016 to 2020
$1.2MAmerican Heart Association-American Stroke Association 15SDG25710438BLRD VA I01 BX000976NHLBI NIH HHS R01 HL112413NHLBI NIH HHS R01 HL127764NHLBI NIH HHS T32 HL007344NIAMS NIH HHS R01 AR071762NIA NIH HHS R01 AG060637NIDDK NIH HHS P30 DK054759NIDDK NIH HHS R01 DK125405NIDDK NIH HHS T32 DK091317NIDDK NIH HHS T32 DK112751NIGMS NIH HHS R25 GM116686
Abstract
Adrenergic stimulation of brown adipocytes alters mitochondrial dynamics, including the mitochondrial fusion protein optic atrophy 1 (OPA1). However, direct mechanisms linking OPA1 to brown adipose tissue (BAT) physiology are incompletely understood. We utilized a mouse model of selective OPA1 deletion in BAT (OPA1 BAT KO) to investigate the role of OPA1 in thermogenesis. OPA1 is required for cold-induced activation of thermogenic genes in BAT. Unexpectedly, OPA1 deficiency induced fibroblast growth factor 21 (FGF21) as a BATokine in an activating transcription factor 4 (ATF4)-dependent manner. BAT-derived FGF21 mediates an adaptive response by inducing browning of white adipose tissue, increasing resting metabolic rates, and improving thermoregulation. However, mechanisms independent of FGF21, but dependent on ATF4 induction, promote resistance to diet-induced obesity in OPA1 BAT KO mice. These findings uncover a homeostatic mechanism of BAT-mediated metabolic protection governed in part by an ATF4-FGF21 axis, which is activated independently of BAT thermogenic function.
Indexed as
Gene DeletionAdipocytes, BrownAdipose Tissue, BrownAdipose Tissue, WhiteAnimalsBody Temperature RegulationFemaleFibroblast Growth FactorsGTP PhosphohydrolasesMaleMiceMice, Inbred C57BLMice, KnockoutObesityfibroblast growth factor 21Fibroblast Growth FactorsGTP PhosphohydrolasesOpa1 protein, mouseactivating transcription factor 4biochemistrybrown adipose tissuebrowningchemical biologyfibroblast growth factor 21mouseoptic atrophy 1thermogenesis
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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.