{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:04:08Z","timestamp":1786122248709,"version":"build-2736575974"},"reference-count":71,"publisher":"Wiley","issue":"44","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Obesity is associated with metabolic disorders due to unhealthy white adipose tissue (WAT) failing to sustain energy homeostasis, highlighting the importance of adipose development. The lactation period is critical for epididymal WAT (eWAT) development and metabolic programming. However, the role of lactoferrin (LF) in the early development of adipose remains unclear. Using a mouse model of lactational LF deficiency and single\u2010nucleus RNA sequencing, we assessed the long\u2010term impact of LF deficiency on eWAT plasticity and metabolic homeostasis at weaning, adulthood, and under a high\u2010fat diet (HFD). LF deficiency persistently impaired eWAT development, causing restricted adipocyte hyperplasia, exacerbated hypertrophy, diminished lipid uptake, and sustained adiponectin decline with resistin elevation. These defects led to long\u2010term metabolic disorders, worsening HFD\u2010induced eWAT remodeling, glucose intolerance, dyslipidemia, and chronic inflammation. Mechanistically, LF could bind CSK and PRMT5. LF promoted CSK degradation, activating SRC to drive preadipocyte proliferation. Additionally, LF stabilized PRMT5 to enhance PPARg\u2010mediated differentiation and lipid uptake. Rescue experiments confirmed that CSK overexpression reversed LF\u2010induced proliferation, while PRMT5 knockdown blocked LF\u2010enhanced differentiation. This study reveals lactational LF as a key nutritional signal that programs adipose development and long\u2010term metabolic health via CSK\u2010SRC and PRMT5\u2010PPARg pathways,\u00a0offering an early\u2010life intervention strategy against obesity\u2010related metabolic diseases.<\/jats:p>","DOI":"10.1002\/advs.75678","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T14:21:58Z","timestamp":1779200518000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lactoferrin Deficiency During Lactation Causes Adult Obesity\u2010Related Metabolic Disease Through Persistent Adipose Dysfunction Driven by Impaired Adipocyte Development"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7766-5883","authenticated-orcid":false,"given":"Qin","family":"An","sequence":"first","affiliation":[{"name":"College of Food Science and Nutritional Engineering China 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