ArticleNature communications2022
Adipocyte-derived lactate is a signalling metabolite that potentiates adipose macrophage inflammation via targeting PHD2.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers, 2 of them syntheses that pooled it.
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Who cites it
117 citing papers in PubMed, 2 syntheses or guidelines pooled it, 151 citations in OpenAlex.
- The lactate-lactylation axis in renal fibrosis: potential mechanisms in diabetic kidney disease.Annals of medicine · 2025Pooled it
- Pooled it
- Multienzymatic hybrid bio-heterojunction for synergistic microenvironment reprogramming and selenoprotein-activated mitochondrial bioenergetics in diabetic osseointegration.Bioactive materials · 2027Article
- Mechanisms of obesogenic adipocyte signaling in mouse 3T3-L1 cells in response to plasma from C57BL/6 mice exposed to traffic-generated emissions and high-fat diet.Toxicology reports · 2026Article
- Liraglutide ameliorates obese type 2 diabetes by regulating macrophage cholesterol metabolism and H3K27ac modification to promote M2 polarization and adipocyte thermogenic activation.Journal of molecular histology · 2026Article
- Lactate Signal: Modulator of Cellular Energy Production and Anabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Roles of inflammation and metabolic dysfunction in cardiovascular diseases: molecular mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Blastocyst-Derived Lactic Acid Regulates Uterine Epithelial Receptivity and Stromal Decidualization via the HIF1α-HO-1-Heme Metabolic Axis.Antioxidants (Basel, Switzerland) · 2026Article
- Redox coupling of lactate and β-hydroxybutyrate: An inter-organ circuit linking metabolic flexibility, mitochondrial adaptation, and disease.Redox biology · 2026Review
- Quercetin Reduces Lipid Accumulation During Adipogenic Differentiation in Association with Stage-Dependent Mitochondrial-Redox and Metabolic Alterations Revealed by Time-ResolvedLife (Basel, Switzerland) · 2026Article
- Integrating Bulk and Single-Cell RNA Sequencing Identifies and Validates Lactylation-Related Signatures in Acute Kidney Injury.Biomedicines · 2026Article
- Methylglyoxal AttenuatesInternational journal of molecular sciences · 2026Article
- Nutritional Status-Based Model for Predicting Low-Lactate Shock: A Retrospective Cohort Study.Shock (Augusta, Ga.) · 2026Article
- Metabolite and nutrient regulation of macrophages in obesity and metabolic disease.Nature reviews. Immunology · 2026Review
- High-salt diet in macrophage-associated metabolic disorders: Mechanisms and therapeutic implications.Chinese medical journal · 2026Review
- Mechanistic Studies of Lactate in Heart Failure: From Metabolic Biomarker to Therapeutic Target.Reviews in cardiovascular medicine · 2026Review
- The role of lactate in retinal health and disease: mechanisms and potential therapeutic strategies. A narrative review.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Review
- Lactate Accelerates Early Angiogenesis and Bone Regeneration Through Macrophage M1 Polarisation.Cell proliferation · 2026Article
- [Lactate induces gastric mucosal injury by promoting M1 polarization of macrophagesNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Mechanistic Insights Into Recurrent Implantation Failure: The Lactate-H3K18la-SLC7A11 Axis Explored via Endometrial Organoid and Blastoid-Endometrial Cell Implantation Models.Cell proliferation · 2026Article
57 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adipose tissue macrophage (ATM) inflammation is involved with meta-inflammation and pathology of metabolic complications. Here we report that in adipocytes, elevated lactate production, previously regarded as the waste product of glycolysis, serves as a danger signal to promote ATM polarization to an inflammatory state in the context of obesity. Adipocyte-selective deletion of lactate dehydrogenase A (Ldha), the enzyme converting pyruvate to lactate, protects mice from obesity-associated glucose intolerance and insulin resistance, accompanied by a lower percentage of inflammatory ATM and reduced production of pro-inflammatory cytokines such as interleukin 1β (IL-1β). Mechanistically, lactate, at its physiological concentration, fosters the activation of inflammatory macrophages by directly binding to the catalytic domain of prolyl hydroxylase domain-containing 2 (PHD2) in a competitive manner with α-ketoglutarate and stabilizes hypoxia inducible factor (HIF-1α). Lactate-induced IL-1β was abolished in PHD2-deficient macrophages. Human adipose lactate level is positively linked with local inflammatory features and insulin resistance index independent of the body mass index (BMI). Our study shows a critical function of adipocyte-derived lactate in promoting the pro-inflammatory microenvironment in adipose and identifies PHD2 as a direct sensor of lactate, which functions to connect chronic inflammation and energy metabolism.
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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.