ArticleMolecular metabolism2022
Loss of UCP1 function augments recruitment of futile lipid cycling for thermogenesis in murine brown fat.
Article in Molecular metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06134258 (Mechanisms of Fasting Induced Reduction in Energy Expenditure - FIRE Trial), which is not on this map. Cited by 55 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Mechanisms of Fasting Induced Reduction in Energy Expenditure - FIRE Trial
Who cites it
55 citing papers in PubMed, 84 citations in OpenAlex.
- The malate-aspartate shuttle supports thermogenic lipid mobilization in brown adipocytes.The FEBS journal · 2026Article
- Evolution of Adaptive Non-Shivering Thermogenesis in Mammals.Physiology (Bethesda, Md.) · 2026Review
- Synergistic Intervention for Obesity: Integrating Central Appetite Regulation and Peripheral Energy Expenditure.Current obesity reports · 2026Review
- Advances in research on thermogenic substances.Journal of physiological anthropology · 2026Review
- Time-restricted feeding improves metabolic flexibility, promotes beiging, and mitigates fibro-inflammation in the adipose tissue of aged mice.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026Article
- Chronic cold exposure induces plasticity of mitochondrial calcium uptake in beige and brown fat of UCP1-deficient mice.bioRxiv : the preprint server for biology · 2026Article
- Gabpα-Pparγ Complex Determines Glycolytic Capacity and Lactic Acid Homeostasis in Brown Fat.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Glycerol and Glycerol-3-Phosphate: Multifaceted Metabolites in Metabolism, Cancer, and Other Diseases.Endocrine reviews · 2026Review
- Advances in Adipose Tissue Biology.Endocrine reviews · 2026Review
- ERα activates NAMPT/IL-33 signaling to enhance beige thermogenesis and metabolic fitness.Science advances · 2026Article
- TMEM120A maintains adipose tissue lipid homeostasis through ER CoA channeling.Nature communications · 2025Article
- The role of immune responses and microbiota in adipose tissue homeostasis.The Journal of physiology · 2025Review
- Brown adipose tissue activity impacts systemic lactate clearance in male mice.The Journal of physiology · 2025Article
- Thermogenic Targets for Obesity Management in the Era of Incretin-Based Therapies.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Whole body MondoA deletion protects against diet-induced obesity through uncontrolled multi-organ substrate utilization and futile cycling.bioRxiv : the preprint server for biology · 2025Article
- Functional Complexity of Thermogenic Adipose Tissue: From Thermogenesis to Metabolic and Fibroinflammatory Crosstalk.International journal of molecular sciences · 2025Review
- Oxidative Phosphorylation in Uncoupled Mitochondria.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Cell and tissue reprogramming: Unlocking a new era in medical drug discovery.Pharmacological reviews · 2025Review
- Intermittent Cold Exposure Induces Distinct Proteomic Signatures in White Adipose Tissue of Mice.International journal of molecular sciences · 2025Article
- Creatine kinase B mediates UCP1-independent beige fat thermogenesis via the futile creatine cycle in mice.Molecular metabolism · 2025Article
Corrections and comments
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Authors and funding
22 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveClassical ATP-independent non-shivering thermogenesis enabled by uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) is activated, but not essential for survival, in the cold. It has long been suspected that futile ATP-consuming substrate cycles also contribute to thermogenesis and can partially compensate for the genetic ablation of UCP1 in mouse models. Futile ATP-dependent thermogenesis could thereby enable survival in the cold even when brown fat is less abundant or missing.
methodsIn this study, we explore different potential sources of UCP1-independent thermogenesis and identify a futile ATP-consuming triglyceride/fatty acid cycle as the main contributor to cellular heat production in brown adipocytes lacking UCP1. We uncover the mechanism on a molecular level and pinpoint the key enzymes involved using pharmacological and genetic interference.
resultsATGL is the most important lipase in terms of releasing fatty acids from lipid droplets, while DGAT1 accounts for the majority of fatty acid re-esterification in UCP1-ablated brown adipocytes. Furthermore, we demonstrate that chronic cold exposure causes a pronounced remodeling of adipose tissues and leads to the recruitment of lipid cycling capacity specifically in BAT of UCP1-knockout mice, possibly fueled by fatty acids from white fat. Quantification of triglyceride/fatty acid cycling clearly shows that UCP1-ablated animals significantly increase turnover rates at room temperature and below.
conclusionOur results suggest an important role for futile lipid cycling in adaptive thermogenesis and total energy expenditure.
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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.