{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T01:39:01Z","timestamp":1772156341176,"version":"3.50.1"},"posted":{"date-parts":[[2023,3,23]]},"group-title":"Developmental Biology","reference-count":66,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The energy-burning capability of beige adipose tissue is a potential therapeutic tool for reducing obesity and metabolic disease, but this capacity is decreased by aging. Here, we evaluate the impact of aging on the profile and activity of adipocyte stem and progenitor cells (ASPCs) and adipocytes during the beiging process. We found that aging increases the expression of\n                  <jats:italic>Cd9<\/jats:italic>\n                  and other fibro-inflammatory genes in fibroblastic ASPCs and blocks their differentiation into beige adipocytes. Fibroblastic ASPC populations from young and aged mice were equally competent for beige differentiation\n                  <jats:italic>in vitro<\/jats:italic>\n                  , suggesting that environmental factors suppress adipogenesis\n                  <jats:italic>in vivo<\/jats:italic>\n                  . Examination of adipocytes by single nucleus RNA-sequencing identified compositional and transcriptional differences in adipocyte populations with age and cold exposure. Notably, cold exposure induced an adipocyte population expressing high levels of\n                  <jats:italic>de novo<\/jats:italic>\n                  lipogenesis (DNL) genes, and this response was severely blunted in aged animals. We further identified natriuretic peptide clearance receptor\n                  <jats:italic>Npr3<\/jats:italic>\n                  , a beige fat repressor, as a marker gene for a subset of white adipocytes and an aging-upregulated gene in adipocytes. In summary, this study indicates that aging blocks beige adipogenesis and dysregulates adipocyte responses to cold exposure and provides a unique resource for identifying cold and aging-regulated pathways in adipose tissue.\n                <\/jats:p>","DOI":"10.1101\/2023.03.20.533514","type":"posted-content","created":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T21:20:23Z","timestamp":1679606423000},"source":"Crossref","is-referenced-by-count":13,"title":["Aging impairs cold-induced beige adipogenesis and adipocyte metabolic reprogramming"],"prefix":"10.64898","author":[{"given":"Corey D.","family":"Holman","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander P.","family":"Sakers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan P.","family":"Calhoun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lan","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ethan C.","family":"Fein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Jacobs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0134-6949","authenticated-orcid":false,"given":"Linus","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evan D.","family":"Rosen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Seale","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024020422450686000_2023.03.20.533514v2.1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/gly290"},{"key":"2024020422450686000_2023.03.20.533514v2.2","doi-asserted-by":"publisher","DOI":"10.1002\/oby.21455"},{"key":"2024020422450686000_2023.03.20.533514v2.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-1126-7"},{"key":"2024020422450686000_2023.03.20.533514v2.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37386-z"},{"key":"2024020422450686000_2023.03.20.533514v2.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.10.023"},{"key":"2024020422450686000_2023.03.20.533514v2.6","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10184"},{"key":"2024020422450686000_2023.03.20.533514v2.7","doi-asserted-by":"publisher","DOI":"10.1172\/JCI59701"},{"key":"2024020422450686000_2023.03.20.533514v2.8","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.3389\/fimmu.2018.02316","article-title":"CD9 Tetraspanin: A New Pathway for the Regulation of Inflammation?","volume":"9","year":"2018","journal-title":"Front Immunol"},{"key":"2024020422450686000_2023.03.20.533514v2.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.05.025"},{"key":"2024020422450686000_2023.03.20.533514v2.10","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00015.2003"},{"key":"2024020422450686000_2023.03.20.533514v2.11","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00474-3"},{"key":"2024020422450686000_2023.03.20.533514v2.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.12.011"},{"key":"2024020422450686000_2023.03.20.533514v2.13","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2018.11.002","article-title":"New Advances in Adaptive Thermogenesis: UCP1 and Beyond","volume":"29","year":"2019","journal-title":"Cell Metab"},{"key":"2024020422450686000_2023.03.20.533514v2.14","doi-asserted-by":"crossref","unstructured":"Chung, M.I. , Bujnis, M. , Barkauskas, C.E. , Kobayashi, Y. , and Hogan, B.L.M . (2018). Niche-mediated BMP\/SMAD signaling regulates lung alveolar stem cell proliferation and differentiation. Development 145.","DOI":"10.1242\/dev.163014"},{"key":"2024020422450686000_2023.03.20.533514v2.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.12.021"},{"key":"2024020422450686000_2023.03.20.533514v2.16","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-19619-0"},{"key":"2024020422450686000_2023.03.20.533514v2.17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1207911109"},{"key":"2024020422450686000_2023.03.20.533514v2.18","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0810780"},{"key":"2024020422450686000_2023.03.20.533514v2.19","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-43130-9"},{"key":"2024020422450686000_2023.03.20.533514v2.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.00310.1101\/746743"},{"key":"2024020422450686000_2023.03.20.533514v2.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2020.09.007"},{"key":"2024020422450686000_2023.03.20.533514v2.22","unstructured":"Fleming, S.J. , Chaffin, M.D. , Arduini, A. , Akkad, A.-D. , Banks, E. , Marioni, J.C. , Philippakis, A.A. , Ellinor, P.T. , and Babadi, M . (2022). CellBender remove-background: a deep generative model for unsupervised removal of background noise from scRNA-seq datasets. bioRxiv."},{"key":"2024020422450686000_2023.03.20.533514v2.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2017.06.001"},{"key":"2024020422450686000_2023.03.20.533514v2.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.10.004"},{"key":"2024020422450686000_2023.03.20.533514v2.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.08.004"},{"key":"2024020422450686000_2023.03.20.533514v2.26","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1111\/iep.12228","article-title":"Ageing is associated with brown adipose tissue remodelling and loss of white fat browning in female C57BL\/6 mice","volume":"98","year":"2017","journal-title":"Int J Exp Pathol"},{"key":"2024020422450686000_2023.03.20.533514v2.27","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12810"},{"key":"2024020422450686000_2023.03.20.533514v2.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.054"},{"key":"2024020422450686000_2023.03.20.533514v2.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.04.011"},{"key":"2024020422450686000_2023.03.20.533514v2.30","doi-asserted-by":"publisher","DOI":"10.1002\/oby.21418"},{"key":"2024020422450686000_2023.03.20.533514v2.31","doi-asserted-by":"publisher","DOI":"10.1038\/srep39794"},{"key":"2024020422450686000_2023.03.20.533514v2.32","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-020-0905-x"},{"key":"2024020422450686000_2023.03.20.533514v2.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.03.025"},{"key":"2024020422450686000_2023.03.20.533514v2.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.01.010"},{"key":"2024020422450686000_2023.03.20.533514v2.35","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14430-w"},{"key":"2024020422450686000_2023.03.20.533514v2.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.12.005"},{"key":"2024020422450686000_2023.03.20.533514v2.37","doi-asserted-by":"crossref","unstructured":"Merrick, D. , Sakers, A. , Irgebay, Z. , Okada, C. , Calvert, C. , Morley, M.P. , Percec, I. , and Seale, P . (2019). Identification of a mesenchymal progenitor cell hierarchy in adipose tissue. Science 364.","DOI":"10.1126\/science.aav2501"},{"key":"2024020422450686000_2023.03.20.533514v2.38","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.060913"},{"key":"2024020422450686000_2023.03.20.533514v2.39","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M050005"},{"key":"2024020422450686000_2023.03.20.533514v2.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2021.03.026"},{"key":"2024020422450686000_2023.03.20.533514v2.41","doi-asserted-by":"publisher","DOI":"10.2337\/db10-0004"},{"key":"2024020422450686000_2023.03.20.533514v2.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.101232"},{"key":"2024020422450686000_2023.03.20.533514v2.43","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12010"},{"key":"2024020422450686000_2023.03.20.533514v2.44","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00473.2013"},{"key":"2024020422450686000_2023.03.20.533514v2.45","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2740"},{"key":"2024020422450686000_2023.03.20.533514v2.46","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.674739"},{"key":"2024020422450686000_2023.03.20.533514v2.47","doi-asserted-by":"publisher","DOI":"10.2337\/db09-0530"},{"key":"2024020422450686000_2023.03.20.533514v2.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.12.016"},{"key":"2024020422450686000_2023.03.20.533514v2.49","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.cmet.2017.10.008","article-title":"Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and Thermogenesis","volume":"27","year":"2018","journal-title":"Cell Metab"},{"key":"2024020422450686000_2023.03.20.533514v2.50","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44271"},{"key":"2024020422450686000_2023.03.20.533514v2.51","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14.10.1345"},{"key":"2024020422450686000_2023.03.20.533514v2.52","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303713200"},{"key":"2024020422450686000_2023.03.20.533514v2.53","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/s42255-021-00373-z","article-title":"Vascular smooth muscle-derived Trpv1(+) progenitors are a source of cold-induced thermogenic adipocytes","volume":"3","year":"2021","journal-title":"Nat Metab"},{"key":"2024020422450686000_2023.03.20.533514v2.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.04.023"},{"key":"2024020422450686000_2023.03.20.533514v2.55","doi-asserted-by":"publisher","DOI":"10.2337\/db19-1874-P"},{"key":"2024020422450686000_2023.03.20.533514v2.56","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0844-1"},{"key":"2024020422450686000_2023.03.20.533514v2.57","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1097\/01.mco.0000171150.49248.14","article-title":"Relationship between body composition changes and changes in physical function and metabolic risk factors in aging","volume":"8","year":"2005","journal-title":"Current Opinion in Clinical Nutrition and Metabolic Care"},{"key":"2024020422450686000_2023.03.20.533514v2.58","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.molmet.2015.11.001","article-title":"EBF2 promotes the recruitment of beige adipocytes in white adipose tissue","volume":"5","year":"2016","journal-title":"Mol Metab"},{"key":"2024020422450686000_2023.03.20.533514v2.59","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3008490"},{"key":"2024020422450686000_2023.03.20.533514v2.60","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3324"},{"key":"2024020422450686000_2023.03.20.533514v2.61","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.05.005"},{"key":"2024020422450686000_2023.03.20.533514v2.62","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.96"},{"key":"2024020422450686000_2023.03.20.533514v2.63","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.05.016"},{"key":"2024020422450686000_2023.03.20.533514v2.64","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2011.125"},{"key":"2024020422450686000_2023.03.20.533514v2.65","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1096\/fj.01-0568com","article-title":"Cold elicits the simultaneous induction of fatty acid synthesis and beta-oxidation in murine brown adipose tissue: prediction from differential gene expression and confirmation in vivo","volume":"16","year":"2002","journal-title":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology"},{"key":"2024020422450686000_2023.03.20.533514v2.66","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14049"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.03.20.533514","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T04:26:29Z","timestamp":1768451189000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.03.20.533514"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,23]]},"references-count":66,"URL":"https:\/\/doi.org\/10.1101\/2023.03.20.533514","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.7554\/eLife.87756","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.87756.3","asserted-by":"object"}],"has-version":[{"id-type":"doi","id":"10.7554\/eLife.87756.2","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.87756.1","asserted-by":"object"}]},"subject":[],"published":{"date-parts":[[2023,3,23]]},"subtype":"preprint"}}