{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:29:37Z","timestamp":1760059777741,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Administration of Traditional Chinese Medicine","award":["zyyzdxk-2023264","82374439","2023-JYB-XJSJJ-017","2025-JYB-JBGS-022","ZJKT2023005"],"award-info":[{"award-number":["zyyzdxk-2023264","82374439","2023-JYB-XJSJJ-017","2025-JYB-JBGS-022","ZJKT2023005"]}]},{"name":"National Natural Science Foundation","award":["zyyzdxk-2023264","82374439","2023-JYB-XJSJJ-017","2025-JYB-JBGS-022","ZJKT2023005"],"award-info":[{"award-number":["zyyzdxk-2023264","82374439","2023-JYB-XJSJJ-017","2025-JYB-JBGS-022","ZJKT2023005"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["zyyzdxk-2023264","82374439","2023-JYB-XJSJJ-017","2025-JYB-JBGS-022","ZJKT2023005"],"award-info":[{"award-number":["zyyzdxk-2023264","82374439","2023-JYB-XJSJJ-017","2025-JYB-JBGS-022","ZJKT2023005"]}]},{"name":"Beijing University of Chinese Medicine","award":["zyyzdxk-2023264","82374439","2023-JYB-XJSJJ-017","2025-JYB-JBGS-022","ZJKT2023005"],"award-info":[{"award-number":["zyyzdxk-2023264","82374439","2023-JYB-XJSJJ-017","2025-JYB-JBGS-022","ZJKT2023005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The hypothalamic-pituitary-adrenal (HPA) axis plays an important regulatory role in inflammatory responses to systemic or local infection in the host. A high-calorie diet, which can aggravate pediatric pneumonia and delay recovery, is intimately associated with HPA axis disorder; however, its underlying mechanisms remain unknown. This study examined whether the mechanism by which a high-calorie diet aggravates pneumonia is related to HPA axis disorder. In this study, juvenile rats were fed a high-calorie diet and\/or nebulized with lipopolysaccharide (LPS) for model construction. Our data shows that a high-calorie diet increases interleukin-1 beta(IL-1\u03b2), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-\u03b1) levels in lung tissues and aggravates LPS-induced inflammatory injury in the lungs of juvenile rats. Additionally, we found that a high-calorie diet decreases the expression level of serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) in juvenile rats with pneumonia, resulting in HPA axis disorder. Hypothalamus proteomics and Western blot results proved that a high-calorie diet upregulated the expression level of hypothalamus hypoxia-inducible factor-1 alpha (HIF-1\u03b1) in juvenile rats with pneumonia, and this mechanism is associated with reduced HIF-1\u03b1 ubiquitination. We further observed that HPA axis disorder was significantly abated and inflammatory damage in rat lung tissues was significantly alleviated after in vivo HIF-1\u03b1 pathway inhibition. This shows that pneumonia aggravation by a high-calorie diet is associated with interference in the HIF-1\u03b1-mediated HPA axis. A high-calorie diet boosts HIF-1\u03b1 signaling in the hypothalamus and exacerbates LPS-induced pneumonia by disrupting the HPA axis. This sheds light on lung inflammation and strengthens the lung-brain connection.<\/jats:p>","DOI":"10.3390\/ijms26146554","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T09:12:48Z","timestamp":1751965968000},"page":"6554","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A High-Calorie Diet Aggravates Lipopolysaccharide-Induced Pulmonary Inflammation in Juvenile Rats via Hypothalamic-Pituitary-Adrenal Axis-Related Pathways"],"prefix":"10.3390","volume":"26","author":[{"given":"Qianqian","family":"Li","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China"},{"name":"School of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250300, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Chinese Medicine Epidemic Disease, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Bai","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Su","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueying","family":"Qin","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiegang","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8361-9455","authenticated-orcid":false,"given":"Xiaohong","family":"Gu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China"},{"name":"Institute of Chinese Medicine Epidemic Disease, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/s41572-021-00259-0","article-title":"Pneumonia","volume":"7","author":"Torres","year":"2021","journal-title":"Nat. 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