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 85 papers, 1 of them a synthesis that pooled it.
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Who cites it
85 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
- Lactate metabolism and protein lactylation in programmed cell death: From novel mechanism to therapeutic strategies in human diseases.Clinical and translational medicine · 2026Review
- Systemic health impact of cancer-associated extracellular vesicles and particles.Nature reviews. Cancer · 2026Review
- An iron-regulated methionine redox axis governs adipose browning and cancer cachexia.Nature cancer · 2026Article
- Impaired liver-muscle lactate metabolism causes sarcopenia via lactic acidosis in skeletal muscle in mice.Science advances · 2026Article
- EIF3H Modulates Glycolysis Through LDHA Stabilization in Triple-Negative Breast Cancer.Cancers · 2026Article
- Therapeutic Gfral silencing via antisense oligonucleotides ameliorates cancer-associated cachexia and extends survival in tumor-bearing mice.Cell reports. Medicine · 2026Article
- 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
- Integrative single-cell and spatial transcriptomic analysis reveals a lactate-driven crosstalk between NFATc4⁺ tumor cells and SPP1⁺ macrophages in glioblastoma.Journal of translational medicine · 2026Article
- 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
- 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
- Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Mechanisms and therapeutic implications of metabolic heterogeneity and histone lactylation in clear cell renal cell carcinoma.Discover oncology · 2026Review
- 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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25 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 OpenQuestion graph.