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The Thermogenic Paradox of Brown Adipose Tissue","","Purpose of Review: Examine how brown adipose tissue (BAT) links obesity, metabolic syndrome, and cancer risk through thermogenesis and adipose browning. Evidence shows a paradox: BAT can support metabolic protection yet also promote tumor progression via tumor-induced thermogenic activation that contributes to cancer-associated cachexia (CAC). Methods include narrative synthesis from 2000–2025 integrating cellular, molecular, and translational mechanisms. Findings highlight transcriptional drivers (PRDM16, PPARγ, PGC1-α) versus tumor-secreted signals (PTHrP, IL-6) inducing UCP1 and β3-adrenergic pathways. Summary: BAT reflects a continuum between protection and pathology with therapeutic relevance for metabolic-oncology.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/fueling-or-fighting-cancer-the-thermogenic-paradox-of-brown-adipose-tissue/353882/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/fueling-or-fighting-cancer-the-thermogenic-paradox-of-brown-adipose-tissue/353882.png","ImageObject",300,407,{"name":92,"@type":93},"Rhys","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"How does brown adipose tissue (BAT) influence cancer risk according to the review?","Question",{"text":113,"@type":114},"BAT can regulate energy metabolism and may modulate cancer risk through thermogenesis and adipose browning. The review emphasizes a paradoxical role where tumor-induced activation may worsen cancer-associated cachexia (CAC).","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What transcriptional pathways are highlighted for adaptive adipose browning?",{"text":118,"@type":114},"Adaptive browning is discussed as being regulated by transcriptional drivers such as PRDM16, PPARγ, and PGC1-α, which can mitigate metabolic inflammation and improve insulin sensitivity, potentially supporting tumor-suppressive effects.",{"name":120,"@type":111,"acceptedAnswer":121},"Which tumor-secreted factors are described as promoting cancer-associated cachexia via thermogenic signaling?",{"text":122,"@type":114},"Tumor-secreted factors including PTHrP and interleukin-6 are reported to aberrantly induce UCP1 expression and β3-adrenergic signaling, driving lipolysis and energy wasting in CAC.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},353882,1790151591,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":56,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},687207024643,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Current Obesity Reports (2026) 15:23  \n[https://doi.org/10.1007/s13679-026-00699-3](https://doi.org/10.1007/s13679-026-00699-3)  \nREVIEW  \nFueling or Fighting Cancer? The Thermogenic Paradox of Brown Adipose Tissue  \nJonathan Jaime G. Guerrero1,2 · Paolo C. Encarnacion1,2 · Chih-Hao Wang3 · Mark Angelo S. del Rosario1 ·  \nKin Israel Notarte4 · Jiayan Zhou5 · Yi-Ta Hsieh6 · Wan-Yu Wang7 · Ching-Wen Chang8,9,10 · Wan-Chun Li11,12,13,14  \nReceived: 7 December 2025 / Accepted: 25 February 2026 © The Author(s) 2026  \nAbstract  \nPurpose of Review The global rise in obesity and metabolic syndrome has intensified interest in brown adipose tissue (BAT) as a regulator of energy metabolism and potential modulator of cancer risk. BAT-mediated thermogenesis and the browning of white adipose tissue (WAT) confer metabolic benefits that may reduce oncogenic susceptibility. However, emerging evidence reveals a paradoxical role for BAT in cancer progression, where tumor-induced thermogenic activation contributes to cancer-associated cachexia (CAC) . This review article examines the cellular, molecular, and translational dimensions of this “thermogenic paradox”.  \nRecent Findings A narrative synthesis was performed using literature from 2000 to 2025 retrieved from PubMed, Scopus, Web of Science, and Google Scholar. Peer-reviewed studies examining the molecular, genetic, and metabolic mechanisms linking BAT or adipose browning to carcinogenesis, obesity-related cancers, and CAC were included. Thematic integration emphasized regulatory pathways, endocrine signaling, and therapeutic implications. Adaptive browning, regulated by transcriptional drivers such as PRDM16, PPARγ, and PGC1-α, mitigates metabolic inflammation, enhances insulin sensitivity, and may exert tumor-suppressive effects. In contrast, tumor-secreted factors including parathyroid hormone-related protein (PTHrP) and interleukin-6 aberrantly induce uncoupling protein 1 (UCP1) expression and β3-adrenergic signaling, driving lipolysis and energy wasting in CAC. The dualistic effects of BAT underscore its context-dependent influence on cancer biology.  \nSummary BAT exemplifies a metabolic continuum between protection and pathology. Clarifying its regulatory mechanisms may inform precision therapies and integrated metabolic-oncology interventions, particularly relevant to low-and middleincome countries facing the double burden of obesity and cachexia.  \nKeywords Adipose browning · Cancer-associated cachexia · Thermogenesis · Metabolic reprogramming · Uncoupling protein 1 · Adipokine signaling  \nIntroduction  \nThe Global cancer burden must be viewed through the lens of the escalating metabolic health crisis. Driven by the soaring prevalence of obesity and metabolic syndrome, nearly three billion people worldwide will be overweight or obese by 2035 [1] . It is well known that obesity and related metabolic disorders, characterized by severe energy imbalance and excess visceral fat accumulation, are potent drivers of carcinogenesis [2–5] . Metabolic dysfunction significantly contributes to the global cancer burden, with  \nExtended author information available on the last page of the article  \nhigh body mass index (BMI) accounting for a significant proportion of adult deaths from Noncommunicable Diseases (NCDs) each year [6, 7] . The contribution of excess body weight to cancer incidence is significant and quantifiable, reaching as high as 10.6% of new cancer cases in women aged 30 and older in the United States in 2019 [8] . This epidemiological risk also exhibits regional heterogeneity: for instance, the Asia-Pacific region reports stronger associations between obesity and both premenopausal and postmenopausal breast cancer [9, 10], and in 2021, Mongolia recorded the world’s highest age-standardized death  \n1 3  \nrate of liver cancer, much of which is attributed to high BMI [11] .  \nCollectively, these global epidemiological patterns point toa unifying biological framework linking metabolic ","cbCaicNId9j8e1dW","https://ap.wps.com/l/cbCaicNId9j8e1dW","pdf",3382670,"English","# Abstract\n## Purpose of Review\n## Recent Findings\n## Summary\n# Introduction","[{\"question\":\"How does brown adipose tissue (BAT) influence cancer risk according to the review?\",\"answer\":\"BAT can regulate energy metabolism and may modulate cancer risk through thermogenesis and adipose browning. The review emphasizes a paradoxical role where tumor-induced activation may worsen cancer-associated cachexia (CAC).\"},{\"question\":\"What transcriptional pathways are highlighted for adaptive adipose browning?\",\"answer\":\"Adaptive browning is discussed as being regulated by transcriptional drivers such as PRDM16, PPARγ, and PGC1-α, which can mitigate metabolic inflammation and improve insulin sensitivity, potentially supporting tumor-suppressive effects.\"},{\"question\":\"Which tumor-secreted factors are described as promoting cancer-associated cachexia via thermogenic signaling?\",\"answer\":\"Tumor-secreted factors including PTHrP and interleukin-6 are reported to aberrantly induce UCP1 expression and β3-adrenergic signaling, driving lipolysis and energy wasting in CAC.\"}]","Fueling or Fighting Cancer? The Thermogenic Paradox of Brown Adipose Tissue | PDF",1790107737,48]