ArticleNature metabolism2024
Activation of GPR81 by lactate drives tumour-induced cachexia.
Article in Nature metabolism, 2024. 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 73 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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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
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- Research trends on lactate in cancer: a bibliometric analysis and comprehensive review (2015-2024).Frontiers in immunology · 2025Pooled it
- Skeletal muscle H3K18 lactylation inhibits hepatic gluconeogenesis through IL-6 mediated interorgan communication.Science advances · 2026Article
- Lactate Biology: Subcellular Routing and Chemical Form Define Function.Biochemistry · 2026Review
- Systemic health impact of cancer-associated extracellular vesicles and particles.Nature reviews. Cancer · 2026Review
- Beyond a waste product: lactate as a master metabolite dictating anti-tumor T-cell fate.Cell death & disease · 2026Review
- Lactate and lactylation in hepatocellular carcinoma: A new frontier in metabolic-epigenetic interactions.Medical oncology (Northwood, London, England) · 2026Review
- PEBP4 alleviates muscle wasting in lung cancer cachexia via KEAP1-NRF2-mediated redox homeostasis.Cell death & disease · 2026Article
- Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Lysine lactylation-mediated post-translational modification: Molecular mechanisms and therapeutic target exploration in tumour drug resistance.Clinical and translational medicine · 2026Review
- Octanoic Acid-Rich Enteral Nutrition Alleviates Sepsis-Associated Metabolic Disorders by Suppressing White Adipose Tissue Browning in Mice.Food science & nutrition · 2026Article
- The impact of lactate and lipid metabolism in microglia upon cognitive impairment following radiation-induced brain injury.Journal of translational medicine · 2026Review
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- Promoting Treg Polarization-Mediated Anti-Scar and Appendage Regeneration in Wound Healing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- FNDC1 Competitively Binds Gβ2 to Suppress the β-Catenin-Destruction Complex and Promote Gastric Cancer Malignancy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- SOD1 lactylation impair its enzymatic activity by conformational change to aggravate intervertebral disc degeneration.Nature communications · 2026Article
- Role of mitochondrial dysfunction in muscle wasting in cancer cachexia: a narrative review.Journal of translational medicine · 2026Review
- Glycolysis enzymes and cellular lactylation in tumour.Clinical and translational medicine · 2026Review
- Inhibiting macrophage-derived lactate transport restores cGAS-STING signalling and enhances antitumour immunity in glioblastoma.Nature cell biology · 2026Article
- Lactate-activated GPR81/FARP1 signaling drives insulin-independent glucose uptake and metabolic control.Cell research · 2026Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
20 authors at 3 institutions in 2 countries.
Funding
Abstract
Cachexia affects 50-80% of patients with cancer and accounts for 20% of cancer-related death, but the underlying mechanism driving cachexia remains elusive. Here we show that circulating lactate levels positively correlate with the degree of body weight loss in male and female patients suffering from cancer cachexia, as well as in clinically relevant mouse models. Lactate infusion per se is sufficient to trigger a cachectic phenotype in tumour-free mice in a dose-dependent manner. Furthermore, we demonstrate that adipose-specific G-protein-coupled receptor (GPR)81 ablation, similarly to global GPR81 deficiency, ameliorates lactate-induced or tumour-induced adipose and muscle wasting in male mice, revealing adipose GPR81 as the major mediator of the catabolic effects of lactate. Mechanistically, lactate/GPR81-induced cachexia occurs independently of the well-established protein kinase A catabolic pathway, but it is mediated by a signalling cascade sequentially activating Gi-Gβγ-RhoA/ROCK1-p38. These findings highlight the therapeutic potential of targeting GPR81 for the treatment of this life-threatening complication of cancer.
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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.