{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:54:44Z","timestamp":1791618884839,"version":"4.3.4"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T00:00:00Z","timestamp":1694044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["111-2314-B-006-101"],"award-info":[{"award-number":["111-2314-B-006-101"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["111-2811-B-006-045"],"award-info":[{"award-number":["111-2811-B-006-045"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Previous studies have shown how adipocytes can modulate the activity of hair follicle stem cells. However, the role of adipocytes in the pathogenesis of androgenetic alopecia (AGA) remains unknown. We aimed to determine signaling pathways related to the adipose tissue changes in the human scalp with AGA through RNA-seq analysis. RNA was isolated from the adipose tissues derived from the bald (frontal) and normal (occipital) scalps of male patients with AGA (<jats:italic>n<\/jats:italic> = 4). The pooled RNA extracts from these samples were subjected to RNA sequencing, followed by differential gene expression and pathway analysis. Our gene expression analysis identified 1,060 differentially expressed genes, including 522 upregulated and 538 downregulated genes in the bald AGA scalp. Biological pathways pertaining to either adipose tissue metabolism or the hair cycle were generated in our pathway analysis. Downregulation of the peroxisome proliferator-activated receptor (PPAR) signaling pathway was noted to be significant in the bald scalp. Expression of adipogenic markers (e.g., <jats:italic>PPARG, FABP4, PLN1<\/jats:italic>, and <jats:italic>ADIPOQ<\/jats:italic>) was also decreased in the bald site. These findings imply that adipogenesis becomes downregulated in AGA, specifically within the bald scalp adipose. Our results lead to the hypothesis that PPAR\u03b3-mediated adipogenesis in the scalp adipose, <jats:italic>via<\/jats:italic> crosstalk with signaling pathways involved in hair cycling, might play a role in AGA.<\/jats:p>","DOI":"10.3389\/fmed.2023.1195656","type":"journal-article","created":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T20:57:30Z","timestamp":1694120250000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Adipose transcriptome in the scalp of androgenetic alopecia"],"prefix":"10.3389","volume":"10","author":[{"given":"Criselda Jean G.","family":"Cruz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Kai","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilson Jr. F.","family":"Aala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren-Yeu","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Lun","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yau-Sheng","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Kai","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Chun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1016\/j.cell.2011.07.019","article-title":"Adipocyte lineage cells contribute to the skin stem cell niche to drive hair cycling","volume":"146","author":"Festa","year":"2011","journal-title":"Cell."},{"key":"B2","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1038\/nature06457","article-title":"Cyclic dermal BMP signalling regulates stem cell activation during hair regeneration","volume":"451","author":"Plikus","year":"2008","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1111\/1523-1747.ep12540633","article-title":"The thickness of human scalp: normal and bald","volume":"58","author":"Hori","year":"1972","journal-title":"J Invest Dermatol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1111\/srt.12908","article-title":"Quantitative analysis of the anatomical changes in the scalp and hair follicles in androgenetic alopecia using magnetic resonance imaging","volume":"27","author":"Soga","year":"2021","journal-title":"Skin Res Technol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"E1501","DOI":"10.1073\/pnas.1312880111","article-title":"Epidermal Wnt\/beta-catenin signaling regulates adipocyte differentiation via secretion of adipogenic factors","volume":"111","author":"Donati","year":"2014","journal-title":"Proc Natl Acad Sci U S A."},{"key":"B6","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1080\/000155500459240","article-title":"Expression of peroxisome proliferator activated receptors (PPARs) in human hair follicles and PPAR alpha involvement in hair growth","volume":"80","author":"Billoni","year":"2000","journal-title":"Acta Derm Venereol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1002\/cyto.a.24569","article-title":"Large-scale isolation of functional dermal papilla cells using novel surface marker LEPTIN Receptor","volume":"101","author":"Gao","year":"2022","journal-title":"Cytometry A."},{"key":"B8","doi-asserted-by":"publisher","first-page":"2611","DOI":"10.1242\/dev.126.12.2611","article-title":"Roles for PDGF-A and sonic hedgehog in development of mesenchymal components of the hair follicle","volume":"126","author":"Karlsson","year":"1999","journal-title":"Development."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1038\/jid.2008.369","article-title":"Hair follicle stem cell-specific PPARgamma deletion causes scarring alopecia","volume":"129","author":"Karnik","year":"2009","journal-title":"J Invest Dermatol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e13790","DOI":"10.15252\/emmm.202013790","article-title":"Discovery of a transdermally deliverable pentapeptide for activating AdipoR1 to promote hair growth","volume":"13","author":"Ohn","year":"2021","journal-title":"EMBO Mol Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1111\/exd.14062","article-title":"PPAR-\u03b3 signalling as a key mediator of human hair follicle physiology and pathology","volume":"29","author":"Ramot","year":"2020","journal-title":"Exper Dermatol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1038\/jid.2013.473","article-title":"Advanced inhibition of undesired human hair growth by PPAR\u03b3 modulation?","volume":"134","author":"Ramot","year":"2014","journal-title":"J Invest Dermatol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1016\/j.jid.2017.09.024","article-title":"Delayed hair follicle morphogenesis and hair follicle dystrophy in a lipoatrophy mouse model of pparg total deletion","volume":"138","author":"Sardella","year":"2018","journal-title":"J Invest Dermatol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2849","DOI":"10.1038\/jid.2012.217","article-title":"Hair growth-promoting effects of adiponectin in vitro","volume":"132","author":"Won","year":"2012","journal-title":"J Invest Dermatol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1111\/exd.12566","article-title":"Leptin of dermal adipose tissue is differentially expressed during the hair cycle and contributes to adipocyte-mediated growth inhibition of anagen-phase vibrissa hair","volume":"24","author":"Yang","year":"2015","journal-title":"Exper Dermatol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1016\/S1097-2765(00)80211-7","article-title":"PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro","volume":"4","author":"Rosen","year":"1999","journal-title":"Mol Cell."},{"key":"B17","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.mce.2016.10.018","article-title":"Androgens modify Wnt agonists\/antagonists expression balance in dermal papilla cells preventing hair follicle stem cell differentiation in androgenetic alopecia","volume":"439","author":"Leir\u00f3s","year":"2017","journal-title":"Mol Cell Endocrinol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2325","DOI":"10.1101\/gad.285429.116","article-title":"Hair follicles' transit-amplifying cells govern concurrent dermal adipocyte production through Sonic Hedgehog","volume":"30","author":"Zhang","year":"2016","journal-title":"Genes Dev."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1633","DOI":"10.1016\/j.jid.2020.12.019","article-title":"Dermal adipose tissue secretes HGF to promote human hair growth and pigmentation","volume":"141","author":"Nicu","year":"2021","journal-title":"J Invest Dermatol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"3837","DOI":"10.1242\/jcs.114.21.3837","article-title":"SPRR4, a novel cornified envelope precursor: UV-dependent epidermal expression and selective incorporation into fragile envelopes","volume":"114","author":"Cabral","year":"2001","journal-title":"J Cell Sci."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2023.1195656\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T20:57:33Z","timestamp":1694120253000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2023.1195656\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,7]]},"references-count":20,"alternative-id":["10.3389\/fmed.2023.1195656"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2023.1195656","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,7]]},"article-number":"1195656"}}