{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:32:24Z","timestamp":1780410744718,"version":"3.54.1"},"reference-count":113,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,5]],"date-time":"2022-11-05T00:00:00Z","timestamp":1667606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia","award":["311\/PPSP\/4404813"],"award-info":[{"award-number":["311\/PPSP\/4404813"]}]},{"name":"Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia","award":["1001.PPSP.8012378"],"award-info":[{"award-number":["1001.PPSP.8012378"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Bee bread (BB) has traditionally been used as a dietary supplement to treat liver problems. This study evaluated the therapeutic effects of Heterotrigona itama BB from Malaysia on obesity-induced hepatic lipid metabolism disorder via the regulation of the Keap1\/Nrf2 pathway. Male Sprague Dawley rats were fed with either a normal diet or high-fat diet (HFD) for 6 weeks to induce obesity. Following 6 weeks, obese rats were treated either with distilled water (OB group), BB (0.5 g\/kg body weight\/day) (OB + BB group) or orlistat (10 mg\/kg body weight\/day) (OB + OR group) concurrent with HFD for another 6 weeks. BB treatment suppressed Keap1 and promoted Nrf2 cytoplasmic and nuclear translocations, leading to a reduction in oxidative stress, and promoted antioxidant enzyme activities in the liver. Furthermore, BB down-regulated lipid synthesis and its regulator levels (SIRT1, AMPK), and up-regulated fatty acid \u03b2-oxidation in the liver of obese rats, being consistent with alleviated lipid levels, improved hepatic histopathological changes (steatosis, hepatocellular hypertrophy, inflammation and glycogen expression) and prevented progression to non-alcoholic steatohepatitis. These results showed the therapeutic potentials of H. itama BB against oxidative stress and improved lipid metabolism in the liver of obese rats possibly by targeting the Keap1\/Nrf2 pathway, hence proposing its role as a natural supplement capable of treating obesity-induced fatty liver disease.<\/jats:p>","DOI":"10.3390\/antiox11112190","type":"journal-article","created":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T02:43:51Z","timestamp":1667789031000},"page":"2190","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Therapeutic Effects of Heterotrigona itama (Stingless Bee) Bee Bread in Improving Hepatic Lipid Metabolism through the Activation of the Keap1\/Nrf2 Signaling Pathway in an Obese Rat Model"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4138-4747","authenticated-orcid":false,"given":"Zaida","family":"Zakaria","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9442-8563","authenticated-orcid":false,"given":"Zaidatul Akmal","family":"Othman","sequence":"additional","affiliation":[{"name":"Unit of Physiology, Universiti Sultan Zainal Abidin, Kuala Terengganu 20400, Terengganu, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0629-7621","authenticated-orcid":false,"given":"Joseph Bagi","family":"Suleiman","sequence":"additional","affiliation":[{"name":"Department of Science Laboratory Technology, Akanu Ibiam Federal Polytechnic, Unwana P.O. Box 1007, Ebonyi State, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9422-005X","authenticated-orcid":false,"given":"Khairul Mohd Fadzli","family":"Mustaffa","sequence":"additional","affiliation":[{"name":"Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur Asyilla Che","family":"Jalil","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan Syaheedah Wan","family":"Ghazali","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ninie Nadia","family":"Zulkipli","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9333-1957","authenticated-orcid":false,"given":"Mahaneem","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia"},{"name":"Unit of Integrative Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaidatul Akmar","family":"Kamaruzaman","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.metabol.2018.09.005","article-title":"The epidemiology of obesity","volume":"92","author":"Chooi","year":"2019","journal-title":"Metabolism"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.ecl.2016.04.004","article-title":"Regarding obesity as a disease: Evolving policies and their implications","volume":"45","author":"Kyle","year":"2016","journal-title":"Endocrinol. 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