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Reduced Insulin Resistance and Oxidative Stress in a Mouse Model of Metabolic Syndrome following Twelve Weeks of Citrus Bioflavonoid Hesperidin Supplementation: A Dose–Response Study

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journal contribution
posted on 2024-06-11, 05:52 authored by Abdulsatar Jamal, Holly Brettle, Dina A Jamil, Vivian TranVivian Tran, Henry Diep, Alexander Bobik, Chris van der Poel, Antony Vinh, Grant R Drummond, Colleen ThomasColleen Thomas, Maria Jelinic, Hayder Al-AubaidyHayder Al-Aubaidy
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 < 0.0001). Fasting blood glucose (FBG) increased by 40% (p < 0.0001), plasma insulin by 100% (p < 0.05), and HOMA-IR by 150% (p < 0.0004), indicating insulin resistance. Hesperidin supplementation reduced plasma insulin by 40% at 140 mg/kg/day (p < 0.0001) and 50% at 280 mg/kg/day (p < 0.005). HOMA-IR decreased by 45% at both doses (p < 0.0001). Plasma hesperidin levels significantly increased in all hesperidin groups (p < 0.0001). Oxidative stress, measured by 8-OHdG, was increased by 40% in HFSS diet mice (p < 0.001) and reduced by 20% with all hesperidin doses (p < 0.005). In conclusion, hesperidin supplementation reduced insulin resistance and oxidative stress in HFSS-fed mice, demonstrating its dose-dependent therapeutic potential in MetS.

Funding

This research was funded by a La Trobe University internal start-up fund (H.A.A.-A.) and a Diabetes Australia Research Program General Grant (MJ, AV, GRD). MJ was supported by a joint National Health and Medical Research Council (NHMRC) and National Heart Foundation of Australia (NHF) Postdoctoral Fellowship (GNT1146314 and 101943). AJ and VT were supported by an Australian Research Training Scholarship.

History

Publication Date

2024-05-29

Journal

Biomolecules

Volume

14

Issue

6

Article Number

637

Pagination

19p.

Publisher

MDPI

ISSN

2218-273X

Rights Statement

© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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