{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T11:24:54Z","timestamp":1777116294944,"version":"3.51.4"},"reference-count":61,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T00:00:00Z","timestamp":1716940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"La Trobe University internal start-up fund","award":["GNT1146314"],"award-info":[{"award-number":["GNT1146314"]}]},{"name":"La Trobe University internal start-up fund","award":["101943"],"award-info":[{"award-number":["101943"]}]},{"name":"a Diabetes Australia Research Program General Grant","award":["GNT1146314"],"award-info":[{"award-number":["GNT1146314"]}]},{"name":"a Diabetes Australia Research Program General Grant","award":["101943"],"award-info":[{"award-number":["101943"]}]},{"name":"a joint National Health and Medical Research Council (NHMRC) and National Heart Foundation of Australia (NHF) Postdoctoral Fellowship","award":["GNT1146314"],"award-info":[{"award-number":["GNT1146314"]}]},{"name":"a joint National Health and Medical Research Council (NHMRC) and National Heart Foundation of Australia (NHF) Postdoctoral Fellowship","award":["101943"],"award-info":[{"award-number":["101943"]}]},{"name":"Australian Research Training Scholarship","award":["GNT1146314"],"award-info":[{"award-number":["GNT1146314"]}]},{"name":"Australian Research Training Scholarship","award":["101943"],"award-info":[{"award-number":["101943"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Metabolic syndrome (MetS) is a cluster of metabolic abnormalities affecting ~25% of adults and is linked to chronic diseases such as cardiovascular disease, cancer, and neurodegenerative diseases. Oxidative stress and inflammation are key drivers of MetS. Hesperidin, a citrus bioflavonoid, has demonstrated antioxidant and anti-inflammatory properties; however, its effects on MetS are not fully established. We aimed to determine the optimal dose of hesperidin required to improve oxidative stress, systemic inflammation, and glycemic control in a novel mouse model of MetS. Male 5-week-old C57BL\/6 mice were fed a high-fat, high-salt, high-sugar diet (HFSS; 42% kcal fat content in food and drinking water with 0.9% saline and 10% high fructose corn syrup) for 16 weeks. After 6 weeks of HFSS, mice were randomly allocated to either the placebo group or low- (70 mg\/kg\/day), mid- (140 mg\/kg\/day), or high-dose (280 mg\/kg\/day) hesperidin supplementation for 12 weeks. The HFSS diet induced significant metabolic disturbances. HFSS + placebo mice gained almost twice the weight of control mice (p &lt; 0.0001). Fasting blood glucose (FBG) increased by 40% (p &lt; 0.0001), plasma insulin by 100% (p &lt; 0.05), and HOMA-IR by 150% (p &lt; 0.0004), indicating insulin resistance. Hesperidin supplementation reduced plasma insulin by 40% at 140 mg\/kg\/day (p &lt; 0.0001) and 50% at 280 mg\/kg\/day (p &lt; 0.005). HOMA-IR decreased by 45% at both doses (p &lt; 0.0001). Plasma hesperidin levels significantly increased in all hesperidin groups (p &lt; 0.0001). Oxidative stress, measured by 8-OHdG, was increased by 40% in HFSS diet mice (p &lt; 0.001) and reduced by 20% with all hesperidin doses (p &lt; 0.005). In conclusion, hesperidin supplementation reduced insulin resistance and oxidative stress in HFSS-fed mice, demonstrating its dose-dependent therapeutic potential in MetS.<\/jats:p>","DOI":"10.3390\/biom14060637","type":"journal-article","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T06:35:32Z","timestamp":1717137332000},"page":"637","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Reduced Insulin Resistance and Oxidative Stress in a Mouse Model of Metabolic Syndrome following Twelve Weeks of Citrus Bioflavonoid Hesperidin Supplementation: A Dose\u2013Response Study"],"prefix":"10.3390","volume":"14","author":[{"given":"Abdulsatar","family":"Jamal","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular Biology and Disease Research, La Trobe Institute for Molecular Science (LIMS), & Department of Microbiology, Anatomy, Physiology & Pharmacology (MAPP), La Trobe University, Bundoora, VIC 3086, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holly","family":"Brettle","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Biology and Disease Research, La Trobe Institute for Molecular Science (LIMS), & Department of Microbiology, Anatomy, Physiology & Pharmacology (MAPP), La Trobe University, Bundoora, VIC 3086, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dina A.","family":"Jamil","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Biology and Disease Research, La Trobe Institute for Molecular Science (LIMS), & Department of Microbiology, Anatomy, Physiology & Pharmacology (MAPP), La Trobe University, Bundoora, VIC 3086, Australia"},{"name":"NewMed Education Australia, Hamilton, QLD 4007, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vivian","family":"Tran","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Biology and Disease Research, La Trobe Institute for Molecular Science (LIMS), & Department of Microbiology, Anatomy, Physiology & Pharmacology (MAPP), La Trobe University, Bundoora, VIC 3086, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry","family":"Diep","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Biology and Disease Research, La Trobe Institute for Molecular Science (LIMS), & Department of Microbiology, Anatomy, Physiology & Pharmacology (MAPP), La Trobe University, Bundoora, VIC 3086, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Bobik","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Biology and Disease Research, La Trobe Institute for Molecular Science (LIMS), & Department of Microbiology, Anatomy, Physiology & Pharmacology (MAPP), La Trobe University, Bundoora, VIC 3086, Australia"},{"name":"Baker Heart and Diabetes Research Institute, Melbourne, VIC 3004, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"van der Poel","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Biology and Disease Research, La Trobe Institute for Molecular Science (LIMS), & Department of Microbiology, Anatomy, Physiology & Pharmacology (MAPP), La Trobe University, Bundoora, VIC 3086, Australia"},{"name":"Australian Institute for Musculoskeletal Science, Melbourne, VIC 3021, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antony","family":"Vinh","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Biology and Disease Research, La Trobe Institute for Molecular Science (LIMS), & Department of Microbiology, Anatomy, Physiology & Pharmacology (MAPP), La Trobe University, Bundoora, VIC 3086, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grant R.","family":"Drummond","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Biology and Disease Research, La Trobe Institute for Molecular Science (LIMS), & Department of Microbiology, Anatomy, Physiology & Pharmacology (MAPP), La Trobe University, Bundoora, VIC 3086, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0457-715X","authenticated-orcid":false,"given":"Colleen J.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Biology and Disease Research, La Trobe Institute for Molecular Science (LIMS), & Department of Microbiology, Anatomy, Physiology & Pharmacology (MAPP), La Trobe University, Bundoora, VIC 3086, Australia"},{"name":"Pre-Clinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Jelinic","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Biology and Disease Research, La Trobe Institute for Molecular Science (LIMS), & Department of Microbiology, Anatomy, Physiology & Pharmacology (MAPP), La Trobe University, Bundoora, VIC 3086, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9564-0120","authenticated-orcid":false,"given":"Hayder A.","family":"Al-Aubaidy","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Biology and Disease Research, La Trobe Institute for Molecular Science (LIMS), & Department of Microbiology, Anatomy, Physiology & Pharmacology (MAPP), La Trobe University, Bundoora, VIC 3086, Australia"},{"name":"NewMed Education Australia, Hamilton, QLD 4007, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1161\/CIRCULATIONAHA.109.192644","article-title":"Harmonizing the metabolic 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