{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:35:40Z","timestamp":1789011340152,"version":"build-2803163510"},"reference-count":53,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T00:00:00Z","timestamp":1734998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Science and Technology","award":["2021R1A2C2007708"],"award-info":[{"award-number":["2021R1A2C2007708"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Type 2 diabetes mellitus (T2DM) is considered a serious risk to public health since its prevalence is rapidly increasing worldwide despite numerous therapeutics. Insulin resistance in T2DM contributes to chronic inflammation and other metabolic abnormalities that generate fat accumulation in the liver, eventually leading to the progression of metabolic dysfunction-associated fatty liver disease (MAFLD). Recently, the possibility that microbial-derived metabolites may alleviate MAFLD through enterohepatic circulation has emerged, but the underlying mechanism remains unclear. In this research, we utilized metabolites obtained from the fermentation of guava leaf extract, which is well-known for its antidiabetic activity, to investigate their effects and mechanisms on MAFLD. Methods: Diabetes was induced by a high-fat diet and streptozotocin injection (80 mg\/kg body weight) twice in mice. Subsequently, mice whose fasting blood glucose levels were measured higher than 300 mg\/dL were administered with metabolites of Limosilactobacillus fermentum (LF) (50 mg\/kg\/day) or guava leaf extract fermented by L. fermentum (GFL) (50 mg\/kg\/day) by gavage for 15 weeks. Results: GFL supplementation mitigated hyperglycemia and hepatic insulin resistance. Moreover, GFL regulated abnormal hepatic histological changes and lipid profiles in diabetic mice. Furthermore, GFL enhanced energy metabolism by activating the sirtuin1 (SIRT1)\/proliferator-activated receptor \u03b3 coactivator 1\u03b1 (PGC1\u03b1)\/peroxisome proliferator-activated receptor (PPAR)-\u03b1 pathway in diabetic mice. Meanwhile, GFL supplementation suppressed hepatic inflammation in diabetic mice. Conclusions: Taken together, the current study elucidated that GFL could be a potential therapeutic to ameliorate hyperglycemia and hepatic steatosis by improving SIRT1\/PGC-1\u03b1\/ PPAR-\u03b1-related energy metabolism in T2DM.<\/jats:p>","DOI":"10.3390\/nu17010007","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T04:45:49Z","timestamp":1735015549000},"page":"7","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Effects of Metabolites Derived from Guava (Psidium guajava L.) Leaf Extract Fermented by Limosilactobacillus fermentum on Hepatic Energy Metabolism via SIRT1-PGC1\u03b1 Signaling in Diabetic Mice"],"prefix":"10.3390","volume":"17","author":[{"given":"Sohyun","family":"Jeon","sequence":"first","affiliation":[{"name":"Department of Food and Nutrition, Kyung Hee University, 26 Kyunghee-Daero, Dongdaemun-Gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heaji","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Kyung Hee University, 26 Kyunghee-Daero, Dongdaemun-Gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8044-5613","authenticated-orcid":false,"given":"Sun-Yeou","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Gachon University, Incheon 21936, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Choong-Hwan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3408-8595","authenticated-orcid":false,"given":"Yunsook","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Kyung Hee University, 26 Kyunghee-Daero, Dongdaemun-Gu, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,24]]},"reference":[{"key":"ref_1","unstructured":"Magliano, D.J., Boyko, E.J., and committee, International Diabetes Federation (IDF) Diabetes Atlas (I.D.A.) 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