ArticleNature communications2025
The Futile Creatine Cycle powers UCP1-independent thermogenesis in classical BAT.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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.
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Who cites it
24 citing papers in PubMed.
- Circulating succinate changes during acute cold exposure are not related with brown adipose tissue in humans.Journal of physiology and biochemistry · 2026Trial
- Changes in circulating bile acid levels during cold exposure are associated with brown adipose tissue in humans: a secondary analysis from the ACTIBATE study.Journal of physiology and biochemistry · 2026Trial
- A nitroalkene derivative of salicylate, SANA, induces creatine-dependent thermogenesis and promotes weight loss.Nature metabolism · 2025Trial
- Gut microbiota contributes to heat tolerance in chickens through metabolic remodeling and suppression of thermogenesis.Poultry science · 2026Article
- Alternative Receptor Signaling for the Selective and Multifaceted Regulation of Human Brown Adipocytes.International journal of molecular sciences · 2026Review
- Article
- Gene Expression Profiling of Adipose Tissue in Enshi Black Pigs Subjected to Cold Stress.Veterinary sciences · 2026Article
- Advances in research on thermogenic substances.Journal of physiological anthropology · 2026Review
- Pharmacological administration of FGF21 reverses obesity through a parabrachial-projecting neuron population in the hindbrain.Cell reports · 2026Article
- Gabpα-Pparγ Complex Determines Glycolytic Capacity and Lactic Acid Homeostasis in Brown Fat.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Pathophysiological Roles of Obesity-Induced Alterations in Extracellular Vesicles Derived from Adipose Tissue and Adipocytes.Current obesity reports · 2026Review
- Review
- ERα activates NAMPT/IL-33 signaling to enhance beige thermogenesis and metabolic fitness.Science advances · 2026Article
- Thermogenic adipose tissue in older adults with obesity: a narrative review of mechanisms, brown fat resistance, and the translational relevance of exercise and nutrition.Frontiers in nutrition · 2026Review
- Brown adipose tissue activity impacts systemic lactate clearance in male mice.The Journal of physiology · 2025Article
- Cold Exposure Induces Swine Brown Adipocytes to Display an Island-like Distribution with Atypical Characteristics.International journal of molecular sciences · 2025Article
- Thermogenic Targets for Obesity Management in the Era of Incretin-Based Therapies.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Article
- Adipose tissue ageing: implications for metabolic health and lifespan.Nature reviews. Endocrinology · 2025Review
- Early adipose tissue wasting in a preclinical model of human lung cancer cachexia.Cell reports · 2025Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Classical brown adipose tissue (BAT) is traditionally viewed as relying exclusively on uncoupling protein 1 (UCP1) for thermogenesis via inducible proton leak. However, the physiological significance of UCP1-independent mechanisms linking substrate oxidation to ATP turnover in classical BAT has remained unclear. Here, we identify the Futile Creatine Cycle (FCC), a mitochondrial-localized energy-wasting pathway involving creatine phosphorylation by creatine kinase b (CKB) and phosphocreatine hydrolysis by tissue-nonspecific alkaline phosphatase (TNAP), as a key UCP1-independent thermogenic mechanism in classical BAT. Reintroducing mitochondrial-targeted CKB exclusively into interscapular brown adipocytes in vivo restores thermogenesis and cold tolerance in mice lacking native UCP1 and CKB, in a TNAP-dependent manner. Furthermore, mice with inducible adipocyte-specific co-deletion of TNAP and UCP1 exhibit severe cold-intolerance. These findings challenge the view that BAT thermogenesis depends solely on UCP1 because of insufficient ATP synthase activity and establishes the FCC as a physiologically relevant thermogenic pathway in classical BAT.
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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 OpenQuestion graph.