{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:48:47Z","timestamp":1786121327939,"version":"build-2736575974"},"reference-count":44,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["520000rmb"],"award-info":[{"award-number":["520000rmb"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["520000rmb"],"award-info":[{"award-number":["520000rmb"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Impaired glucose tolerance (IGT) is a prediabetic condition affecting over 600 million adults worldwide. Mulberry leaf (Morus alba L.) has shown antidiabetic potential, but whether adipose AMPK\u03b11 is required for its effects remains unclear. This study aimed to determine whether mulberry leaf water extract (MLE) ameliorates IGT through adipose AMPK\u03b11-mediated gut microbiota modulation and thermogenesis. Methods: Adipose-specific AMPK\u03b11 knockout (AKO) mice and floxed controls (Flox) were fed a high-fat diet for 12 weeks to establish IGT, then treated with MLE or short-chain fatty acids (SCFAs) for 10 weeks. Metabolic parameters, gut microbiota (16S rRNA sequencing), fecal SCFAs, and AMPK\u03b11\/SIRT1\/PGC-1\u03b1 pathway expression were assessed. Results: In Flox mice, MLE and SCFAs significantly improved glucose tolerance, reduced serum lipids and hepatic steatosis, and enhanced brown adipose tissue activation and white adipose browning. These effects were accompanied by gut microbiota remodeling, elevated fecal acetate\/propionate\/butyrate, and upregulation of the AMPK\u03b11\/SIRT1\/PGC-1\u03b1 pathway. All these metabolic and microbiota benefits were abrogated in AKO mice, in which MLE failed to improve any parameter, with only minimal and functionally insignificant thermogenic gene\/protein upregulation. Conclusions: Adipose AMPK\u03b11 is essential for MLE to improve IGT via gut microbiota\/SCFAs and thermogenesis. These findings identify adipose AMPK\u03b11 as a molecular target for dietary intervention in prediabetes.<\/jats:p>","DOI":"10.3390\/ph19081232","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:16:29Z","timestamp":1785935789000},"page":"1232","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mulberry Leaf Water Extract Ameliorates Impaired Glucose Tolerance via the Gut Microbiota\/SCFAs\/AMPK\u03b11 Axis in Adipose Tissue"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0713-0502","authenticated-orcid":false,"given":"Yang","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yige","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhang","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiamei","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuchang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaiting","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sitong","family":"Bu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongcheng","family":"An","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menglu","family":"Wang","sequence":"additional","affiliation":[{"name":"Certification Center for Licensed Pharmacist of NMPA, Beijing 100061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Shan","sequence":"additional","affiliation":[{"name":"Amway (China) Co., Ltd., Beijing 517399, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baosheng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.2337\/dbi25-0006","article-title":"Pathobiology of Prediabetes: Understanding and Interrupting Progressive Dysglycemia and Associated Complications","volume":"74","year":"2025","journal-title":"Diabetes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e13598","DOI":"10.1111\/1753-0407.13598","article-title":"Influence of impaired glucose tolerance alone and combined with metabolic syndrome on long-term risk of cardiovascular events and mortality","volume":"16","author":"Chen","year":"2024","journal-title":"J. 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