{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:13:24Z","timestamp":1787026404152,"version":"build-2736575974"},"reference-count":95,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>\n                    Bone remodeling is orchestrated by osteoclast-mediated resorption and osteoblast-mediated formation. Dysregulated hyperactivity of osteoclasts is a central driver of pathological bone loss in multiple osteolytic diseases, such as postmenopausal osteoporosis, rheumatoid arthritis, and peri-implant osteolysis. Although the core RANKL signaling cascade that governs osteoclast differentiation has been well characterized, accumulating evidence indicates that RANKL also triggers profound metabolic reprogramming during osteoclastogenesis, among which fatty acid (FA) metabolism has emerged as a critical regulator of osteoclast fate and function. In this review, we provide a comprehensive analysis of how FA metabolic pathways regulate osteoclast differentiation, fusion, and function. We first briefly introduce the core FA metabolic pathways relevant to osteoclasts, including FA uptake, FA oxidation, FA storage,\n                    <jats:italic>de novo<\/jats:italic>\n                    lipogenesis, and protein S-palmitoylation. We then examine their specific roles in osteoclastogenesis, focusing on the key regulators (namely FATP2, FABP4, CD36, FASN, ACC1, CPT1A, and DGAT1). Furthermore, we evaluate the translational potential of targeting these metabolic nodes for treating osteolytic diseases, and discuss key challenges, including paradoxical stage-dependent functions of FA oxidation, off-target and species-specific toxicities of systemic inhibitors, and the necessity of osteoclast-specific delivery strategies. Finally, we identify critical knowledge gaps and propose future directions. Collectively, targeting osteoclastic FA metabolism offers a promising, yet challenging, therapeutic avenue for osteolytic diseases.\n                  <\/jats:p>","DOI":"10.3389\/fendo.2026.1887006","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T14:40:12Z","timestamp":1784731212000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Regulation of osteoclastogenesis and bone resorption by fatty acid metabolism: mechanisms and therapeutic opportunities"],"prefix":"10.3389","volume":"17","author":[{"given":"Yingying","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine, School of Medicine, Hangzhou City University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanchan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, School of Medicine, Hangzhou City University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyan","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, School of Medicine, Hangzhou City University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zichen","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, School of Medicine, Hangzhou City University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianquan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, School of Medicine, Hangzhou City University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1038\/s44324-024-00010-9","article-title":"Bone metabolism - an underappreciated player","volume":"2","author":"Choi","year":"2024","journal-title":"NPJ Metab Health Dis"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-031521-040919","article-title":"Osteoclasts, master sculptors of bone","volume":"18","author":"Veis","year":"2023","journal-title":"Annu Rev Pathol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2025.1670716","article-title":"Osteocytes: master orchestrators of skeletal homeostasis, remodeling, and osteoporosis pathogenesis","volume":"13","author":"Wu","year":"2025","journal-title":"Front Cell Dev Biol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.01.001","article-title":"Parathyroid hormone directs bone marrow mesenchymal cell fate","volume":"25","author":"Fan","year":"2017","journal-title":"Cell Metab"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.7554\/elife.78496","article-title":"Lipolysis of bone marrow adipocytes is required to fuel bone and the marrow niche during energy deficits","volume":"11","author":"Li","year":"2022","journal-title":"Elife"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.7150\/thno.95423","article-title":"Osteoblast-specific down-regulation of NLRP3 inflammasome by aptamer-functionalized liposome nanoparticles improves bone quality in postmenopausal osteoporosis rats","volume":"14","author":"Xu","year":"2024","journal-title":"Theranostics"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-018-2817-9","article-title":"Mechanisms involved in normal and pathological osteoclastogenesis","volume":"75","author":"Park-Min","year":"2018","journal-title":"Cell Mol Life Sci"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202000771r","article-title":"Both aerobic glycolysis and mitochondrial respiration are required for osteoclast differentiation","volume":"34","author":"Li","year":"2020","journal-title":"FASEB J"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.997358","article-title":"Mitochondrial fatty acid beta-oxidation is important for normal osteoclast formation in growing female mice","volume":"13","author":"Kushwaha","year":"2022","journal-title":"Front Physiol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2025.156186","article-title":"Pharmacologically targeting fatty acid synthase-mediated de novo lipogenesis alleviates osteolytic bone loss by directly inhibiting osteoclastogenesis through suppression of STAT3 palmitoylation and ROS signaling","volume":"167","author":"Xiu","year":"2025","journal-title":"Metabolism"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1172\/jci89935","article-title":"MYC-dependent oxidative metabolism regulates osteoclastogenesis via nuclear receptor ERRalpha","volume":"127","author":"Bae","year":"2017","journal-title":"J Clin Invest"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s44319-024-00255-x","article-title":"Glutaminolysis provides nucleotides and amino acids to regulate osteoclast differentiation in mice","volume":"25","author":"Hu","year":"2024","journal-title":"EMBO Rep"},{"key":"B13","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/s41413-024-00374-0","article-title":"Metabolic reprogramming in skeletal cell differentiation","volume":"12","author":"Bertels","year":"2024","journal-title":"Bone Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-023-00948-y","article-title":"The serine synthesis pathway drives osteoclast differentiation through epigenetic regulation of NFATc1 expression","volume":"6","author":"Stegen","year":"2024","journal-title":"Nat Metab"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.838664","article-title":"CPT1A-mediated fatty acid oxidation promotes precursor osteoclast fusion in rheumatoid arthritis","volume":"13","author":"Huang","year":"2022","journal-title":"Front Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2019.02.017","article-title":"Treatment with an inhibitor of fatty acid synthase attenuates bone loss in ovariectomized mice","volume":"122","author":"Bermeo","year":"2019","journal-title":"Bone"},{"key":"B17","doi-asserted-by":"publisher","first-page":"4437","DOI":"10.1038\/s41467-025-59719-w","article-title":"FABP4 inhibition suppresses bone resorption and protects against postmenopausal osteoporosis in ovariectomized mice","volume":"16","author":"Xie","year":"2025","journal-title":"Nat Commun"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgad355","article-title":"The multifaceted roles of bone marrow adipocytes in bone and hematopoietic homeostasis","volume":"108","author":"Li","year":"2023","journal-title":"J Clin Endocrinol Metab"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.09.015","article-title":"Lipids in the bone marrow: an evolving perspective","volume":"31","author":"Rendina-Ruedy","year":"2020","journal-title":"Cell Metab"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-032122-030352","article-title":"Fatty acid transport and signaling: mechanisms and physiological implications","volume":"85","author":"Samovski","year":"2023","journal-title":"Annu Rev Physiol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.tibs.2025.09.005","article-title":"Molecular mechanisms of the mammalian fatty acid cycle","volume":"51","author":"Gusenda","year":"2026","journal-title":"Trends Biochem Sci"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/jbmr\/zjae034","article-title":"FATP2 regulates osteoclastogenesis by increasing lipid metabolism and ROS production","volume":"39","author":"Kong","year":"2024","journal-title":"J Bone Miner Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-024-01036-5","article-title":"Inhibition of fatty acid uptake by TGR5 prevents diabetic cardiomyopathy","volume":"6","author":"Wang","year":"2024","journal-title":"Nat Metab"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2012.02.010","article-title":"Peroxisomal acyl-CoA synthetases","volume":"1822","author":"Watkins","year":"2012","journal-title":"Biochim Biophys Acta"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v13.i11.1512","article-title":"Fatty acid metabolism and acyl-CoA synthetases in the liver-gut axis","volume":"13","author":"Ma","year":"2021","journal-title":"World J Hepatol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1038\/s41573-021-00367-2","article-title":"Lipogenesis inhibitors: therapeutic opportunities and challenges","volume":"21","author":"Batchuluun","year":"2022","journal-title":"Nat Rev Drug Discov"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2025.102264","article-title":"Isotype-selective roles of hepatic acetyl-CoA carboxylases in a mouse model of fatty liver disease","volume":"102","author":"Beretta","year":"2025","journal-title":"Mol Metab"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1172\/jci182480","article-title":"Acetyl-CoA carboxylase 1 inhibition increases Treg metabolism and graft-versus-host disease treatment efficacy via mitochondrial fusion","volume":"135","author":"McDonald-Hyman","year":"2025","journal-title":"J Clin Invest"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1172\/jci27300","article-title":"Reversal of diet-induced hepatic steatosis and hepatic insulin resistance by antisense oligonucleotide inhibitors of acetyl-CoA carboxylases 1 and 2","volume":"116","author":"Savage","year":"2006","journal-title":"J Clin Invest"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-08782-w","article-title":"Structural dynamics of human fatty acid synthase in the condensing cycle","volume":"641","author":"Choi","year":"2025","journal-title":"Nature"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2025.109050","article-title":"The ELOVL proteins: very and ultra long-chain fatty acids at the crossroads between metabolic and neurodegenerative disorders","volume":"144","author":"Ferrero","year":"2025","journal-title":"Mol Genet Metab"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlr.2025.100824","article-title":"Stearoyl-CoA desaturase 1 deficiency drives saturated lipid accumulation and increases liver and plasma acylcarnitines","volume":"66","author":"Kalyesubula","year":"2025","journal-title":"J Lipid Res"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.fmre.2024.09.011","article-title":"Targeting fatty acid metabolism for cancer therapy","volume":"6","author":"Zhang","year":"2026","journal-title":"Fundam Res"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlr.2024.100604","article-title":"Etomoxir: an old dog with new tricks","volume":"65","author":"McGuffee","year":"2024","journal-title":"J Lipid Res"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqz046","article-title":"CPT1A-mediated fat oxidation, mechanisms, and therapeutic potential","volume":"161","author":"Schlaepfer","year":"2020","journal-title":"Endocrinology"},{"key":"B36","doi-asserted-by":"publisher","first-page":"13933","DOI":"10.3390\/ijms232213933","article-title":"Mitochondrial fatty acid beta-oxidation disorders: from disease to lipidomic studies-a critical review","volume":"23","author":"Guerra","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-023-00845-0","article-title":"Lipid droplet biogenesis and functions in health and disease","volume":"19","author":"Zadoorian","year":"2023","journal-title":"Nat Rev Endocrinol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-018-0085-z","article-title":"Dynamics and functions of lipid droplets","volume":"20","author":"Olzmann","year":"2019","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-024-01364-4","article-title":"Lipid droplets and cellular lipid flux","volume":"26","author":"Mathiowetz","year":"2024","journal-title":"Nat Cell Biol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.64046","article-title":"Lipid-induced S-palmitoylation as a vital regulator of cell signaling and disease development","volume":"17","author":"Qu","year":"2021","journal-title":"Int J Biol Sci"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.148281","article-title":"The emerging role of palmitoyl acyltransferase zDHHC5 in health and disease: a review","volume":"330","author":"Xiu","year":"2025","journal-title":"Int J Biol Macromol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.101920","article-title":"Control of mitochondria-associated endoplasmic reticulum membranes by protein S-palmitoylation: novel therapeutic targets for neurodegenerative diseases","volume":"87","author":"He","year":"2023","journal-title":"Ageing Res Rev"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2025.117232","article-title":"S-palmitoylation in bone biology: emerging insights and therapeutic potential","volume":"242","author":"Ji","year":"2025","journal-title":"Biochem Pharmacol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-023-00825-3","article-title":"Novel insights into osteoclast energy metabolism","volume":"21","author":"Ledesma-Colunga","year":"2023","journal-title":"Curr Osteoporos Rep"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2150","article-title":"Palmitic acid and DGAT1 deficiency enhance osteoclastogenesis, while oleic acid-induced triglyceride formation prevents it","volume":"29","author":"Drosatos-Tampakaki","year":"2014","journal-title":"J Bone Miner Res"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.m800626","article-title":"Saturated fatty acids enhance osteoclast survival","volume":"51","author":"Oh","year":"2010","journal-title":"J Lipid Res"},{"key":"B47","doi-asserted-by":"publisher","first-page":"441","DOI":"10.3390\/nu9050441","article-title":"Palmitoleic acid inhibits RANKL-induced osteoclastogenesis and bone resorption by suppressing NF-kappaB and MAPK signalling pathways","volume":"9","author":"van Heerden","year":"2017","journal-title":"Nutrients"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2003.18.7.1206","article-title":"Dietary n-3 fatty acids decrease osteoclastogenesis and loss of bone mass in ovariectomized mice","volume":"18","author":"Sun","year":"2003","journal-title":"J Bone Miner Res"},{"key":"B49","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/s41467-017-02490-4","article-title":"Short-chain fatty acids regulate systemic bone mass and protect from pathological bone loss","volume":"9","author":"Lucas","year":"2018","journal-title":"Nat Commun"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.037200","article-title":"The scavenger receptor CD36 plays a role in cytokine-induced macrophage fusion","volume":"122","author":"Helming","year":"2009","journal-title":"J Cell Sci"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.ra117.000633","article-title":"The contribution of cross-talk between the cell-surface proteins CD36 and CD47-TSP-1 in osteoclast formation and function","volume":"293","author":"Koduru","year":"2018","journal-title":"J Biol Chem"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.2574","article-title":"A CD36-binding peptide from thrombospondin-1 can stimulate resorption by osteoclasts in vitro","volume":"270","author":"Carron","year":"2000","journal-title":"Biochem Biophys Res Commun"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2025.168139","article-title":"Neutrophil-derived thrombospondin-1 (THBS1) drives type 2 diabetes-induced osteoporosis via CD36-PPARgamma-POU2F2 signaling","volume":"1872","author":"Huang","year":"2026","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.2139\/ssrn.5254757","article-title":"Fabkin promoted osteoclasts mature and bone loss in OVX-induced osteoporosis mice","volume":"39","author":"Pan","year":"2025","journal-title":"FASEB J"},{"key":"B55","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41413-022-00211-2","article-title":"FABP4 secreted by M1-polarized macrophages promotes synovitis and angiogenesis to exacerbate rheumatoid arthritis","volume":"10","author":"Guo","year":"2022","journal-title":"Bone Res"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2023.07.001","article-title":"Targeting Kindlin-2 in adipocytes increases bone mass through inhibiting FAS\/PPARgamma\/FABP4 signaling in mice","volume":"13","author":"Tang","year":"2023","journal-title":"Acta Pharm Sin B"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202403177","article-title":"PRMT6 epigenetically drives metabolic switch from fatty acid oxidation toward glycolysis and promotes osteoclast differentiation during osteoporosis","volume":"11","author":"Chu","year":"2024","journal-title":"Adv Sci (Weinh)"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2025.107092","article-title":"Fatty acid binding protein 2 (FATP2\/SLC27A2) blockade with Lipofermata elicits dual effects on inflammatory responses in human monocytes and macrophages","volume":"277","author":"Hahn","year":"2026","journal-title":"Immunol Lett"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.08.055","article-title":"Fatty acid transport protein-2 inhibitor Grassofermata\/CB5 protects cells against lipid accumulation and toxicity","volume":"465","author":"Saini","year":"2015","journal-title":"Biochem Biophys Res Commun"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201600825rrr","article-title":"REV-ERB agonism suppresses osteoclastogenesis and prevents ovariectomy-induced bone loss partially via FABP4 upregulation","volume":"32","author":"Song","year":"2018","journal-title":"FASEB J"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.12.050","article-title":"Succinimidyl oleate, established inhibitor of CD36\/FAT translocase inhibits complex III of mitochondrial respiratory chain","volume":"391","author":"Drahota","year":"2010","journal-title":"Biochem Biophys Res Commun"},{"key":"B62","doi-asserted-by":"publisher","first-page":"9104","DOI":"10.1038\/s41598-024-58689-1","article-title":"SMS121, a new inhibitor of CD36, impairs fatty acid uptake and viability of acute myeloid leukemia","volume":"14","author":"Abacka","year":"2024","journal-title":"Sci Rep"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1101\/2024.09.13.612932","article-title":"CD11B+CD36+ cells are bone anabolic macrophages that limit age-associated bone loss","author":"Koroth","year":"2024","journal-title":"bioRxiv"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlr.2024.100611","article-title":"Etomoxir-carnitine, a novel pharmaco-metabolite of etomoxir, inhibits phospholipases A(2) and mitochondrial respiration","volume":"65","author":"Moon","year":"2024","journal-title":"J Lipid Res"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1042\/cs20060307","article-title":"A double-blind randomized multicentre clinical trial to evaluate the efficacy and safety of two doses of etomoxir in comparison with placebo in patients with moderate congestive heart failure: the ERGO (etomoxir for the recovery of glucose oxidation) study","volume":"113","author":"Holubarsch","year":"2007","journal-title":"Clin Sci (Lond)"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1021\/jm020979u","article-title":"Discovery of a long-chain carbamoyl aminocarnitine derivative, a reversible carnitine palmitoyltransferase inhibitor with antiketotic and antidiabetic activity","volume":"46","author":"Giannessi","year":"2003","journal-title":"J Med Chem"},{"key":"B67","doi-asserted-by":"publisher","first-page":"3624","DOI":"10.3390\/molecules28083624","article-title":"Perhexiline: Old drug, new tricks? A summary of its anti-cancer effects","volume":"28","author":"Dhakal","year":"2023","journal-title":"Molecules"},{"key":"B68","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1016\/j.cmet.2017.07.009","article-title":"Acetyl CoA carboxylase inhibition reduces hepatic steatosis but elevates plasma triglycerides in mice and humans: A bedside to bench investigation","volume":"26","author":"Kim","year":"2017","journal-title":"Cell Metab"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.782","article-title":"Safety, tolerability, pharmacokinetics, and pharmacodynamics of a liver-targeting acetyl-CoA carboxylase inhibitor (PF-05221304): A three-part randomized phase 1 study","volume":"9","author":"Bergman","year":"2020","journal-title":"Clin Pharmacol Drug Dev"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1520686113","article-title":"Acetyl-CoA carboxylase inhibition by ND-630 reduces hepatic steatosis, improves insulin sensitivity, and modulates dyslipidemia in rats","volume":"113","author":"Harriman","year":"2016","journal-title":"Proc Natl Acad Sci USA"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.08.020","article-title":"Inhibition of acetyl-CoA carboxylase by phosphorylation or the inhibitor ND-654 suppresses lipogenesis and hepatocellular carcinoma","volume":"29","author":"Lally","year":"2019","journal-title":"Cell Metab"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4181","article-title":"Inhibition of acetyl-CoA carboxylase suppresses fatty acid synthesis and tumor growth of non-small-cell lung cancer in preclinical models","volume":"22","author":"Svensson","year":"2016","journal-title":"Nat Med"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-00272-9","article-title":"De novo lipogenesis is essential for platelet production in humans","volume":"2","author":"Kelly","year":"2020","journal-title":"Nat Metab"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c00640","article-title":"Optimizing the benefit\/risk of acetyl-CoA carboxylase inhibitors through liver targeting","volume":"63","author":"Huard","year":"2020","journal-title":"J Med Chem"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2019.03.023","article-title":"Design and synthesis of a novel 1H-pyrrolo[3,2-b]pyridine-3-carboxamide derivative as an orally available ACC1 inhibitor","volume":"27","author":"Mizojiri","year":"2019","journal-title":"Bioorg Med Chem"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2018.05.055","article-title":"Discovery of a novel olefin derivative as a highly potent and selective acetyl-CoA carboxylase 2 inhibitor with in vivo efficacy","volume":"28","author":"Nishiura","year":"2018","journal-title":"Bioorg Med Chem Lett"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-08587-x","article-title":"Snapshots of acyl carrier protein shuttling in human fatty acid synthase","volume":"641","author":"Schultz","year":"2025","journal-title":"Nature"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.7.3450","article-title":"Synthesis and antitumor activity of an inhibitor of fatty acid synthase","volume":"97","author":"Kuhajda","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"key":"B79","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1042\/bj20041963","article-title":"Characterization of the inactivation of rat fatty acid synthase by C75: inhibition of partial reactions and protection by substrates","volume":"388","author":"Rendina","year":"2005","journal-title":"Biochem J"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m310991200","article-title":"C75, a fatty acid synthase inhibitor, modulates AMP-activated protein kinase to alter neuronal energy metabolism","volume":"279","author":"Landree","year":"2004","journal-title":"J Biol Chem"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0500619102","article-title":"Effect of centrally administered C75, a fatty acid synthase inhibitor, on ghrelin secretion and its downstream effects","volume":"102","author":"Hu","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0801639","article-title":"Influence of orlistat on bone turnover and body composition","volume":"25","author":"Gotfredsen","year":"2001","journal-title":"Int J Obes Relat Metab Disord"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1808834116","article-title":"Inhibition of de novo lipogenesis targets androgen receptor signaling in castration-resistant prostate cancer","volume":"116","author":"Zadra","year":"2019","journal-title":"Proc Natl Acad Sci USA"},{"key":"B84","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1038\/s41389-023-00460-8","article-title":"Involvement of the pro-oncogenic enzyme fatty acid synthase in the hallmarks of cancer: a promising target in anti-cancer therapies","volume":"12","author":"Vanauberg","year":"2023","journal-title":"Oncogenesis"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2021.100797","article-title":"First-in-human study of the safety, pharmacokinetics, and pharmacodynamics of first-in-class fatty acid synthase inhibitor TVB-2640 alone and with a taxane in advanced tumors","volume":"34","author":"Falchook","year":"2021","journal-title":"EClinicalMedicine"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14272","article-title":"Inhibition of fatty acid synthase with FT-4101 safely reduces hepatic de novo lipogenesis and steatosis in obese subjects with non-alcoholic fatty liver disease: Results from two early-phase randomized trials","volume":"23","author":"Beysen","year":"2021","journal-title":"Diabetes Obes Metab"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2016.04.011","article-title":"Fasnall, a selective FASN inhibitor, shows potent anti-tumor activity in the MMTV-Neu model of HER2(+) breast cancer","volume":"23","author":"Alwarawrah","year":"2016","journal-title":"Cell Chem Biol"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1603","article-title":"A human fatty acid synthase inhibitor binds beta-ketoacyl reductase in the keto-substrate site","volume":"10","author":"Hardwicke","year":"2014","journal-title":"Nat Chem Biol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2020.105321","article-title":"Evaluation of FASN inhibitors by a versatile toolkit reveals differences in pharmacology between human and rodent FASN preparations and in antiproliferative efficacy in vitro vs. in situ in human cancer cells","volume":"149","author":"Singha","year":"2020","journal-title":"Eur J Pharm Sci"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noaf098","article-title":"S-palmitoylation of c-MET by CK2alpha-mediated zDHHC15 phosphorylation drives glioblastoma stem cell tumorigenicity","volume":"27","author":"Wang","year":"2025","journal-title":"Neuro Oncol"},{"key":"B91","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jot.2023.06.002","article-title":"Pharmacological inhibition of protein S-palmitoylation suppresses osteoclastogenesis and ameliorates ovariectomy-induced bone loss","volume":"42","author":"Ma","year":"2023","journal-title":"J Orthop Translat"},{"key":"B92","doi-asserted-by":"publisher","first-page":"11415","DOI":"10.3390\/ijms252111415","article-title":"2-Bromopalmitate-induced intestinal flora changes and testicular dysfunction in mice","volume":"25","author":"Ma","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-019-0375-6","article-title":"Inhibiting PD-L1 palmitoylation enhances T-cell immune responses against tumours","volume":"3","author":"Yao","year":"2019","journal-title":"Nat BioMed Eng"},{"key":"B94","doi-asserted-by":"publisher","first-page":"4642","DOI":"10.1038\/s41467-024-49105-3","article-title":"ZDHHC20-mediated S-palmitoylation of YTHDF3 stabilizes MYC mRNA to promote pancreatic cancer progression","volume":"15","author":"Zhang","year":"2024","journal-title":"Nat Commun"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae973","article-title":"Generic Diagramming Platform (GDP): a comprehensive database of high-quality biomedical graphics","volume":"53","author":"Jiang","year":"2025","journal-title":"Nucleic Acids Res"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1887006\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T14:40:14Z","timestamp":1784731214000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1887006\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,22]]},"references-count":95,"alternative-id":["10.3389\/fendo.2026.1887006"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1887006","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,22]]},"article-number":"1887006"}}