{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:43:02Z","timestamp":1790480582842,"version":"4.1.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"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:sec><jats:title>Background<\/jats:title><jats:p>Obesity has become a significant public health issue, yet its underlying mechanisms remain complex. The hypothalamus, a crucial part of the central nervous system, plays a vital role in maintaining energy balance. Disruptions in hypothalamic homeostasis can lead to obesity and related metabolic disorders. Recent studies have increasingly focused on the role of intercellular interactions within the hypothalamus in obesity development, though the exact mechanisms are still under investigation. Mast cells, as innate immune cells, have been linked to obesity, but their specific roles and mechanisms require further exploration. This study aims to investigate whether hypothalamic mast cells influence microglia and subsequently affect metabolic homeostasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted experiments to examine the effects of high-fat diets on mast cells in the arcuate nucleus of the hypothalamus. We analyzed the activation of microglia and the activity of POMC neurons in response to mast cell activation. The study involved feeding mice a high-fat diet and then assessing changes in mast cell populations, microglial activation, and neuronal activity in the hypothalamus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our findings indicate that high-fat feeding increases the number of mast cells in the arcuate nucleus of the hypothalamus. These mast cells activate microglia, which in turn suppress the activity of POMC neurons. This suppression promotes appetite and reduces energy expenditure, leading to obesity. The results suggest a direct role of hypothalamic mast cells in the regulation of energy balance and obesity development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This study highlights the regulatory role of mast cells in the hypothalamus in the formation of obesity. By activating microglia and influencing POMC neuron activity, mast cells contribute to metabolic dysregulation. These findings provide a new target for the treatment of obesity and related metabolic diseases, emphasizing the importance of hypothalamic immune interactions in metabolic health. Further research is needed to explore the potential therapeutic applications of targeting mast cells in obesity management.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1544213","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T05:19:23Z","timestamp":1742534363000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Mast cell promotes obesity by activating microglia in hypothalamus"],"prefix":"10.3389","volume":"16","author":[{"given":"Wen","family":"Tian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1186\/1471-2458-14-233","article-title":"Obesogenic environments: a systematic review of the association between the physical environment and adult weight status, the SPOTLIGHT project","volume":"14","author":"Mackenbach","year":"2014","journal-title":"BMC Public Health"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-019-0176-8","article-title":"Obesity: global epidemiology and pathogenesis","volume":"15","author":"Bl\u00fcher","year":"2019","journal-title":"Nat Rev Endocrinol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R700005-JLR200","article-title":"Thematic review series: Adipocyte Biology. Adipose tissue function and plasticity orchestrate nutritional adaptation","volume":"48","author":"Sethi","year":"2007","journal-title":"J Lipid Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.v27.8","article-title":"Mast cell stabilization: novel medication for obesity and diabetes","volume":"27","author":"Wang","year":"2011","journal-title":"Diabetes\/metabol Res Rev"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2007.00520.x","article-title":"Mast cells in the promotion and limitation of chronic inflammation","volume":"217","author":"Metz","year":"2007","journal-title":"Immunol Rev"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1994","article-title":"Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice","volume":"15","author":"Liu","year":"2009","journal-title":"Nat Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00110","article-title":"Mast cell neural interactions in health and disease","volume":"13","author":"Mittal","year":"2019","journal-title":"Front Cell Neurosci"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2023.10.032","article-title":"Mast cells in the autonomic nervous system and potential role in disorders with dysautonomia and neuroinflammation","volume":"132","author":"Theoharides","year":"2024","journal-title":"Ann allergy Asthma Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22031093","article-title":"Decoding mast cell-microglia communication in neurodegenerative diseases","volume":"22","author":"Sandhu","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B10","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1016\/j.cmet.2019.08.010","article-title":"Microglial UCP2 mediates inflammation and obesity induced by high-fat feeding","volume":"30","author":"Kim","year":"2019","journal-title":"Cell Metab"},{"key":"B11","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.immuni.2021.12.012","article-title":"Metabolic adaptation of lymphocytes in immunity and disease","volume":"55","author":"Chapman","year":"2022","journal-title":"Immunity"},{"key":"B12","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.immuni.2020.08.012","article-title":"Systemic immunometabolism: challenges and opportunities","volume":"53","author":"Lercher","year":"2020","journal-title":"Immunity"},{"key":"B13","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1007\/s13238-021-00834-x","article-title":"The hypothalamus for whole-body physiology: from metabolism to aging","volume":"13","author":"Liu","year":"2022","journal-title":"Protein Cell"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3217","article-title":"From neuroanatomy to behavior: central integration of peripheral signals regulating feeding behavior","volume":"15","author":"Williams","year":"2012","journal-title":"Nat Neurosci"},{"key":"B15","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.cmet.2017.05.015","article-title":"Microglial inflammatory signaling orchestrates the hypothalamic immune response to dietary excess and mediates obesity susceptibility","volume":"26","author":"Valdearcos","year":"2017","journal-title":"Cell Metab"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24217","article-title":"Long-term priming of hypothalamic microglia is associated with energy balance disturbances under diet-induced obesity","volume":"70","author":"Fern\u00e1ndez-Arjona","year":"2022","journal-title":"Glia"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3390\/nu13020498","article-title":"The role of hypothalamic inflammation in diet-induced obesity and its association with cognitive and mood disorders","volume":"13","author":"Dionysopoulou","year":"2021","journal-title":"Nutrients"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2017.02.005","article-title":"Obesity-induced neuroinflammation: beyond the hypothalamus","volume":"40","author":"Guillemot-Legris","year":"2017","journal-title":"Trends Neurosci"},{"key":"B19","doi-asserted-by":"publisher","first-page":"109951","DOI":"10.1016\/j.neuropharm.2024.109951","article-title":"Rethinking the role of microglia in obesity","volume":"253","author":"Cutugno","year":"2024","journal-title":"Neuropharmacology"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.12659\/MSMBR.893093","article-title":"Mast cells and neuroinflammation","volume":"20","author":"Dong","year":"2014","journal-title":"Med Sci monitor basic Res"},{"key":"B21","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s12986-021-00569-w","article-title":"STAT3 phosphorylation in central leptin resistance","volume":"18","author":"Liu","year":"2021","journal-title":"Nutr Metab"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1111\/all.2013.68.issue-4","article-title":"Mast cell activation syndromes: definition and classification","volume":"68","author":"Valent","year":"2013","journal-title":"Allergy"},{"key":"B23","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/all.12126","article-title":"Mast cells and basophils","volume":"16","author":"Schwartz","year":"2002","journal-title":"Clin Allergy Immunol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1111\/all.2019.74.issue-1","article-title":"Mast cell disorders: From infancy to maturity","volume":"74","author":"Wilcock","year":"2019","journal-title":"Allergy"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1042\/CS20100459","article-title":"Mast cells in health and disease","volume":"120","author":"Weller","year":"2011","journal-title":"Clin Sci (London England: 1979)"},{"key":"B26","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1196\/nyas.2008.1143.issue-1","article-title":"Mast cells: multifaceted immune cells with diverse roles in health and disease","volume":"1143","author":"Rao","year":"2008","journal-title":"Ann New York Acad Sci"},{"key":"B27","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.brainres.2007.07.034","article-title":"Brain mast cell relationship to neurovasculature during development","volume":"1171","author":"Khalil","year":"2007","journal-title":"Brain Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/nri1460","article-title":"Mast-cell responses to pathogens","volume":"4","author":"Marshall","year":"2004","journal-title":"Nat Rev Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.2174\/092986707780597961","article-title":"Microglial activation and its implications in the brain diseases","volume":"14","author":"Dheen","year":"2007","journal-title":"Curr med Chem"},{"key":"B30","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.tem.2012.11.004","article-title":"CNS insulin signaling in the control of energy homeostasis and glucose metabolism - from embryo to old age","volume":"24","author":"Vogt","year":"2013","journal-title":"Trends Endocrinol Metabol: TEM"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1544213\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T05:19:26Z","timestamp":1742534366000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1544213\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,21]]},"references-count":30,"alternative-id":["10.3389\/fendo.2025.1544213"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1544213","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,21]]},"article-number":"1544213"}}