ArticleCell reports2019
A GPR17-cAMP-Lactate Signaling Axis in Oligodendrocytes Regulates Whole-Body Metabolism.
Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 65 citations in OpenAlex.
- Tmem117, an oligodendrocyte-enriched regulator of NCX activity, links myelin homeostasis to counterregulation and metabolic health.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- G Protein-Coupled Receptor 17 (Gpr17) Enhances Leptin and Insulin Sensitivity in Lean and Obese Mouse Models.Obesity (Silver Spring, Md.) · 2026Review
- Selective GPR17 antagonism enhances structural and functional recovery in animal models of demyelination.PloS one · 2026Article
- Review
- Recent advances in reprogramming lactate metabolism in polycystic ovary syndrome.Journal of ovarian research · 2025Review
- Microbiome affects mice metabolic homeostasis via differential regulation of gene expression in the brain and gut.Physiological reports · 2025Article
- Review
- Histone lactylation mediated by Fam172a in POMC neurons regulates energy balance.Nature communications · 2024Article
- Respiratory infection with influenza A virus delays remyelination and alters oligodendrocyte metabolism.iScience · 2024Article
- Exercise-induced appetite suppression: An update on potential mechanisms.Physiological reports · 2024Review
- Revealing brain cell-stratified causality through dissecting causal variants according to their cell-type-specific effects on gene expression.Nature communications · 2024Article
- The anorectic and thermogenic effects of pharmacological lactate in male mice are confounded by treatment osmolarity and co-administered counterions.Nature metabolism · 2023Article
- Coordinated Regulation of Myelination by Growth Factor and Amino-acid Signaling Pathways.Neuroscience bulletin · 2023Review
- Malocclusion impairs cognitive behavior via AgRP signaling in adolescent mice.Frontiers in neuroscience · 2023Article
- Cryo-EM structure of G-protein-coupled receptor GPR17 in complex with inhibitory G protein.MedComm · 2022Article
- SP and KLF Transcription Factors in Cancer Metabolism.International journal of molecular sciences · 2022Review
- Leukotrienes vs. Montelukast-Activity, Metabolism, and Toxicity Hints for Repurposing.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Article
- Glial cells as integrators of peripheral and central signals in the regulation of energy homeostasis.Nature metabolism · 2022Review
- Glial Modulation of Energy Balance: The Dorsal Vagal Complex Is No Exception.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
The CNS plays a pivotal role in energy homeostasis, but whether oligodendrocytes are involved has been largely unexplored. Here, we show that signaling through GPR17, a G-protein-coupled receptor predominantly expressed in the oligodendrocyte lineage, regulates food intake by modulating hypothalamic neuronal activities. GPR17-null mice and mice with an oligodendrocyte-specific knockout of GPR17 have lean phenotypes on a high-fat diet, suggesting that GPR17 regulates body weight by way of oligodendrocytes. Downregulation of GPR17 results in activation of cAMP-protein kinase A (PKA) signaling in oligodendrocytes and upregulated expression of pyruvate dehydrogenase kinase 1 (PDK1), which promotes lactate production. Elevation of lactate activates AKT and STAT3 signaling in the hypothalamic neurons, leading to increased expression of Pomc and suppression of Agrp. Our findings uncover a critical role of oligodendrocytes in metabolic homeostasis, where GPR17 modulates the production of lactate, which, in turn, acts as a metabolic signal to regulate neuronal activity.
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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.