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This review explores the emerging concept of bidirectional crosstalk between BAT and pancreatic \u03b2-cells, focusing on potential mechanisms through which BAT may regulate insulin secretion and \u03b2-cell survival. In addition to its thermogenic function, BAT serves as a metabolic sink and secretes various hormones (batokines), metabolites, and exosomes that can influence \u03b2-cell function directly or indirectly. Key batokines such as fibroblast growth factor 21, IL-6, ependymin-related protein 1, neuregulin 4, and phospholipid-transfer protein have shown potential in the preservation of \u03b2-cell health, although their clinical relevance requires further investigation. Emerging evidence also points to BAT-derived exosomes and microRNAs, including miR-26a, as novel regulators of insulin secretion. Neural mechanisms may contribute to this interorgan communication via sympathetic and sensory innervation, and BAT-derived neurotrophic factors may modulate autonomic inputs to peripheral tissues, including the pancreas. Conversely, \u03b2-cells influence BAT activation via hormonal (eg, insulin, glucagon), exosomal, and central pathways, forming a proposed BAT-brain-islet axis. This bidirectional communication appears disrupted in obesity and diabetes, where BAT dysfunction and \u03b2-cell stress exacerbate metabolic decline. Despite growing interest, mechanistic insights into BAT-islet crosstalk remain incomplete. Future research using omics technologies, co-culture systems, and in vivo manipulation models will be critical to identify novel mediators and clarify their roles in metabolic regulation. Understanding this interorgan communication may offer new therapeutic avenues for obesity and diabetes.<\/jats:p>","DOI":"10.1210\/endocr\/bqaf118","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T14:11:16Z","timestamp":1752502276000},"source":"Crossref","is-referenced-by-count":11,"title":["Emerging Insights into Brown Adipose Tissue Crosstalk With Pancreatic \u03b2-Cells in Metabolic Regulation"],"prefix":"10.1210","volume":"166","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4766-6375","authenticated-orcid":false,"given":"Chenxu","family":"Yan","sequence":"first","affiliation":[{"name":"Neuroendocrinology Group, Garvan Institute of Medical Research, St Vincent's Hospital , Sydney, NSW 2010 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2560-3604","authenticated-orcid":false,"given":"George","family":"Burley","sequence":"additional","affiliation":[{"name":"Neuroendocrinology Group, Garvan Institute of Medical Research, St Vincent's Hospital , Sydney, NSW 2010 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanyu","family":"Gao","sequence":"additional","affiliation":[{"name":"Neuroendocrinology Group, Garvan Institute of Medical Research, St Vincent's Hospital , Sydney, NSW 2010 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8368-6735","authenticated-orcid":false,"given":"Yan-Chuan","family":"Shi","sequence":"additional","affiliation":[{"name":"Neuroendocrinology Group, Garvan Institute of Medical Research, St Vincent's Hospital , Sydney, NSW 2010 ,","place":["Australia"]},{"name":"Faculty of Medicine and Health, UNSW Sydney , Sydney 2052 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"issue":"12","key":"2025072505321222900_bqaf118-B1","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1038\/s42255-019-0148-2","article-title":"Integrating the inputs that shape pancreatic islet hormone release","volume":"1","author":"Noguchi","year":"2019","journal-title":"Nat Metab"},{"key":"2025072505321222900_bqaf118-B2","doi-asserted-by":"crossref","first-page":"155709","DOI":"10.1016\/j.metabol.2023.155709","article-title":"Brown adipose tissue-derived metabolites and their role in regulating metabolism","volume":"150","author":"Ziqubu","year":"2024","journal-title":"Metabolism"},{"issue":"Pt 4","key":"2025072505321222900_bqaf118-B3","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1242\/jcs.103.4.931","article-title":"Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization","volume":"103","author":"Cousin","year":"1992","journal-title":"J Cell Sci"},{"issue":"1","key":"2025072505321222900_bqaf118-B4","doi-asserted-by":"crossref","first-page":"2622","DOI":"10.1038\/s41467-021-22925-3","article-title":"Peripheral-specific Y1 receptor antagonism increases thermogenesis and protects against diet-induced obesity","volume":"12","author":"Yan","year":"2021","journal-title":"Nat Commun"},{"issue":"1","key":"2025072505321222900_bqaf118-B5","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1210\/endrev\/bnz007","article-title":"Brown adipose crosstalk in tissue plasticity and human metabolism","volume":"41","author":"Scheele","year":"2020","journal-title":"Endocr Rev"},{"issue":"15","key":"2025072505321222900_bqaf118-B6","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1056\/NEJMoa0808949","article-title":"Functional brown adipose tissue in healthy adults","volume":"360","author":"Virtanen","year":"2009","journal-title":"N Engl J Med"},{"issue":"15","key":"2025072505321222900_bqaf118-B7","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1056\/NEJMoa0810780","article-title":"Identification and importance of brown adipose tissue in adult humans","volume":"360","author":"Cypess","year":"2009","journal-title":"N Engl J Med"},{"issue":"15","key":"2025072505321222900_bqaf118-B8","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1056\/NEJMoa0808718","article-title":"Cold-activated brown adipose tissue in healthy men","volume":"360","author":"van Marken Lichtenbelt","year":"2009","journal-title":"N Engl J Med"},{"issue":"5982","key":"2025072505321222900_bqaf118-B9","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1126\/science.1190816","article-title":"Medicine. 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