{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T12:00:33Z","timestamp":1784289633158,"version":"3.55.0"},"reference-count":42,"publisher":"Wiley","issue":"45","license":[{"start":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270101"],"award-info":[{"award-number":["82270101"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Obesity\u2010associated obstructive sleep apnea (OSA) highlights the need for effective therapies. Hypothalamic endoplasmic reticulum (ER) stress contributes to leptin resistance in obesity. Although hesperidin (HE) modulates ER stress and oxidative pathways, its low bioavailability limits clinical use, its role in OSA is unknown. Self\u2010assembled HE nanoparticles (HE NPs) are developed to address this. HE NPs are synthesized via solvent emulsification\u2010evaporation and tested in diet\u2010induced obese (DIO), lean, and\u00a0ob\/ob\u00a0mice. In DIO mice, HE NPs reduce food intake, body weight, and plasma leptin while mitigating hypothalamic ER stress and boosting STAT3 phosphorylation, without toxicity, and they outperform HE and PLGA NPs. In\u00a0ob\/ob\u00a0mice, HE NPs lower PERK phosphorylation and, with leptin, further suppress weight gain and food intake while enhancing STAT3 signaling. Combining HE NPs with leptin in DIO mice amplifies weight loss versus HE NPs alone. HE NPs also improve sleep\u2010disordered breathing, lowering the apnea index during non\u2010rapid eye movement sleep (17.1\u00b13.5 to 9.3\u00b13.0 events h\n                    <jats:sup>\u22121<\/jats:sup>\n                    ,\u00a0\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt; 0.01) and rapid eye movement sleep (22.4\u00b15.6 to 12.8\u00b13.9 events h\n                    <jats:sup>\u22121<\/jats:sup>\n                    ,\u00a0\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt; 0.05). The results demonstrate that HE NPs improve metabolic dysfunction and OSA in obesity by reducing ER stress and restoring leptin sensitivity, offering a novel therapeutic strategy.\n                  <\/jats:p>","DOI":"10.1002\/advs.202506182","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T10:28:03Z","timestamp":1757413683000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Targeted Delivery of CNS\u2010Specific Hesperidin as a Leptin Sensitizer for Treating Obesity\u2010Associated Sleep\u2010Disordered Breathing"],"prefix":"10.1002","volume":"12","author":[{"given":"Yixuan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Renmin Hospital of Wuhan University  Wuhan Hubei 430060 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