Quercetin and nanoquercetin mitigate high fat diet-induced obesity via lipid modulation, genomic DNA integrity restoration, adipokine regulation, and hepato-pancreatic tissue preservation.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Quercetin*/pharmacology ; Quercetin*/administration & dosage ; Obesity*/drug therapy ; Obesity*/metabolism ; Obesity*/etiology ; Obesity*/pathology ; Diet, High-Fat*/adverse effects ; Pancreas*/drug effects ; Pancreas*/metabolism ; Pancreas*/pathology ; Liver*/drug effects ; Liver*/metabolism ; Liver*/pathology ; Adipokines*/metabolism ; Lipid Metabolism*/drug effects ; Anti-Obesity Agents*/pharmacology; Nanoparticles/chemistry ; Body Weight/drug effects ; Lipids/blood ; Animals ; Male ; Rats ; Rats, Wistar

Obesity is a global health challenge characterized by excessive fat accumulation and associated with life-threatening comorbidities such as type 2 diabetes, cardiovascular diseases, and certain cancers. Conventional treatments, including lifestyle modification and pharmacotherapy, often have limited long-term efficacy and potential side effects, highlighting the need for safer alternatives. Natural bioactive compounds, such as quercetin, a dietary flavonoid with antioxidant, anti-inflammatory, and metabolic regulatory properties, have emerged as promising anti-obesity agents. However, poor bioavailability limits its therapeutic application, prompting the development of nanoformulations. This study therefore estimated the anti-obesity potential of quercetin and nanoquercetin in a high-fat diet (HFD)-induced obesity model in male Wistar rats. Following acute toxicity testing, 36 rats were divided into six groups: non-obese control, obese HFD control, and non-obese or obese rats orally received quercetin or nanoquercetin at 10% of the safe dose daily for four weeks. Outcomes assessed included body weight, lipid profile, serum total protein, genomic DNA integrity, Adiponectin and Leptin gene expression, and histological changes in liver and pancreatic tissues. In non-obese rats, quercetin and nanoquercetin did not affect body weight and genomic DNA integrity but improved lipid profiles. Nanoquercetin additionally increased total protein levels. Both compounds upregulated Adiponectin expression in the liver, with nanoquercetin also enhancing pancreatic Adiponectin expression. Histology revealed preserved tissue architecture. In obese rats, administration of quercetin or nanoquercetin significantly reduced body weight, improved lipid and protein parameters, restored genomic DNA integrity, upregulated Adiponectin, downregulated Leptin, and markedly improved hepatic and pancreatic histological architecture. Nanoquercetin consistently produced more pronounced effects than quercetin.nIn. These findings demonstrate the therapeutic potential of quercetin, particularly its nanoform, as a multi-targeted anti-obesity agent. Its effects on metabolic regulation, genomic protection, and tissue preservation support further preclinical and clinical studies to explore its role as a safe and effective strategy for managing obesity.
(© 2026. The Author(s).)

Declarations. Competing interests: The authors declare no competing interests. Ethics declaration: All procedures involving animals were conducted in accordance with ethical standards for the care and use of laboratory animals following the guidelines of the National Institutes of Health (NIH, 2011) and were approved by the Institutional Animal Care and Use Committee (IACUC) in Egypt, under accreditation number CU/I/F/13/21.

World Health Organization. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser. 894(i-xii), 1–253. PMID: 11234459. (2000). https://pubmed.ncbi.nlm.nih.gov/11234459/.
Ng, M., Fleming, T., Robinson, M., Thomson, B., Graetz, N., Margono, C., … Gakidou,E. x Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: A systematic analysis for the Global Burden of Disease Study 2013. The Lancet, 384(9945), 766–781. 10–11.
World Health Organization. Obesity and overweight. (2025). https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.
Calle, E. E. & Kaaks, R. Overweight, obesity and cancer: Epidemiological evidence and proposed mechanisms. Nat. Rev. Cancer 4(8), 579–91. https://doi.org/10.1038/nrc1408 (2004). (PMID: 10.1038/nrc140815286738)
Kahn, S. E., Hull, R. L. & Utzschneider, K. M. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444(7121), 840–6. https://doi.org/10.1038/nature05482 (2006). (PMID: 10.1038/nature0548217167471)
Stefan, N., Häring, H. U. & Cusi, K. Non-alcoholic fatty liver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies. Lancet Diabetes Endocrinol. 7(4):313–324. doi: 10.1016/S2213–8587(18)30154–2. Epub 2018 Aug 30. PMID: 30174213. (2019).
Atlantis, E. & Baker, M. Obesity effects on depression: Systematic review of epidemiological studies. Int. J. Obes. (Lond.) 32(6), 881–91. https://doi.org/10.1038/ijo.2008.54 (2008). (PMID: 10.1038/ijo.2008.5418414420)
Guh, D. P. et al. The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health. 9(88). (2009). https://doi.org/10.1186/1471-2458-9–88 . PMID: 19320986; PMCID: PMC2667420.
Park, J., Euhus, D. M. & Scherer, P. E. Paracrine and endocrine effects of adipose tissue on cancer development and progression. Endocr Rev. 2011;32(4):550–70. doi: 10.1210/er.2010–0030. Epub 2011 Jun 2. PMID: 21642230; PMCID: PMC3369575. (2011).
World Health Organization. Global health risks: Mortality and burden of disease attributable to selected major risks (WHO, 2009).
Scully, T., Ettela, A., LeRoith, D. & Gallagher, E. J. Obesity, Type 2 Diabetes, and Cancer Risk. Front Oncol. 10:615375. (2020). https://doi.org/10.3389/fonc.2020.615375 . PMID: 33604295; PMCID: PMC7884814.
Bray, G. A., Frühbeck, G., Ryan, D. H. & Wilding, J. P. Management of obesity. Lancet. 2016;387(10031):1947–56. doi: 10.1016/S0140–6736(16)00271–3. Epub 2016 Feb 10. PMID: 26868660. (2016).
Martel, J. et al. Anti-obesogenic and antidiabetic effects of plants and mushrooms. Nat. Rev. Endocrinol. 13(3), 149–160. https://doi.org/10.1038/nrendo.2016.142 (2017). (PMID: 10.1038/nrendo.2016.14227636731)
Boots, A. W., Haenen, G. R. & Bast, A. Health effects of quercetin: From antioxidant to nutraceutical. Eur. J. Pharmacol. 13(2–3), 325–37. https://doi.org/10.1016/j.ejphar.2008.03.008 (2008). (PMID: 10.1016/j.ejphar.2008.03.008)
Li, Y. et al. Quercetin, inflammation and immunity. Nutrients 15(3), 167. https://doi.org/10.3390/nu8030167 (2016). (PMID: 10.3390/nu8030167)
Kumar, S. & Pandey, A. K. Chemistry and biological activities of flavonoids: An overview. Sci. World J. 2013(1), 162750. https://doi.org/10.1155/2013/162750 (2013). (PMID: 10.1155/2013/162750)
Manach, C., Williamson, G., Morand, C., Scalbert, A. & Rémésy, C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am. J. Clin. Nutr. 81(1 Suppl), 230S-242S. https://doi.org/10.1093/ajcn/81.1.230S (2005). (PMID: 10.1093/ajcn/81.1.230S15640486)
Dabeek, W. M. & Marra, M. V. Dietary quercetin and kaempferol: Bioavailability and potential cardiovascular-related bioactivity in humans. Nutrients 25(10), 2288. https://doi.org/10.3390/nu11102288 (2019). (PMID: 10.3390/nu11102288)
D’Andrea, G. Quercetin: A flavonol with multifaceted therapeutic applications?. Fitoterapia 106, 256–271. https://doi.org/10.1016/j.fitote.2015.09.018 (2015). (PMID: 10.1016/j.fitote.2015.09.01826393898)
Hanhineva, K. et al. Impact of dietary polyphenols on carbohydrate metabolism. Int. J. Mol. Sci. 11(4), 1365–1402. https://doi.org/10.3390/ijms11041365 (2010). (PMID: 10.3390/ijms11041365204800252871121)
Williamson, G. The role of polyphenols in modern nutrition. Nutr. Bull. 42 (3), 226–235. https://doi.org/10.1111/nbu.12278 (2017). (PMID: 10.1111/nbu.12278289831925601283)
El-Sayed, H. S., Selim, A. O., Azab, D. M. & Tawfik, W. A. Evaluation of the antibacterial effect of quercetin nanoparticles (QUENPS) on drug-resistant Escherichia coli strains in rabbits. Egypt. J. Agric. Res. 99(1), 94–107 (2021).
Reed, M. J. et al. A new rat model of type 2 diabetes: The fat-fed, streptozotocin-treated rat. Metab. Clin. Exp. 49(11), 1390–1394. https://doi.org/10.1053/meta.2000.17721 (2000). (PMID: 10.1053/meta.2000.1772111092499)
Wali, J. A. et al. Cardio-metabolic effects of high-fat diets and their underlying mechanisms-A narrative review. Nutrients 21, 1505. https://doi.org/10.3390/nu12051505 (2020). (PMID: 10.3390/nu12051505)
Tice, R. R. et al. Single cell gel/comet assay: Guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 35, 206–221 (2000). (PMID: 10.1002/(SICI)1098-2280(2000)35:3<206::AID-EM8>3.0.CO;2-J10737956)
Mohamed, H. R. H., Ibrahim, M. M. H., Soliman, E. S. M., Safwat, G. & Diab, A. Estimation of Calcium Titanate or Erbium Oxide Nanoparticles Induced Cytotoxicity and Genotoxicity in Normal HSF Cells. Biol Trace Elem Res. 2023;201(5):2311–2318. (2023). https://doi.org/10.1007/s12011-022-03354–9 . Epub 2022 Jul 30. PMID: 35907160; PMCID: PMC10020245.
Joffin, N. et al. Citrulline induces fatty acid release selectively in visceral adipose tissue from old rats. Mol. Nutr. Food Res. 58 (2014)), pp1765–1775 (2014). (PMID: 10.1002/mnfr.201400053)
Joffin, N. et al. Acute induction of uncoupling protein 1 by citrulline in cultured explants of white adipose tissue from lean and high-fat-diet-fed rats. Adipocyte 4 (2015), 129–134 (2015). (PMID: 10.4161/21623945.2014.989748261674164497294)
Livak, K. J. & Schmittgen, T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25(4), 402–8. https://doi.org/10.1006/meth.2001.1262 (2001). (PMID: 10.1006/meth.2001.126211846609)
Jensenv, K. Theory and practice of histological techniques, 6th edition. J. Neuropathol. Exp. Neurol. 67(6), 633. https://doi.org/10.1097/NEN.0b013e31817e2933 (2008). (PMID: 10.1097/NEN.0b013e31817e2933)
Bray, G. A., Kim, K. K. & Wilding, J. P. H. Obesity: A chronic relapsing progressive disease process. A position statement of the World Obesity Federation. Obes. Rev. 18(7), 715–723. https://doi.org/10.1111/obr.12551 (2017). (PMID: 10.1111/obr.1255128489290)
Srivastava, G. & Apovian, C. M. Current pharmacotherapy for obesity. Nat. Rev. Endocrinol. 14(1), 12–24. https://doi.org/10.1038/nrendo.2017.122 (2018). (PMID: 10.1038/nrendo.2017.12229027993)
Blüher, M. Obesity: Global epidemiology and pathogenesis. Nat. Reviews Endocrinol. 15 (5), 288–298. https://doi.org/10.1038/s41574-019-0176–8 (2019).
Jiang, H. et al. Drug-induced oxidative stress in cancer treatments: Angel or devil?. Redox Biol. 63, 102754. https://doi.org/10.1016/j.redox.2023.102754 (2023).
Roy, A. et al. Flavonoids a bioactive compound from medicinal plants and its therapeutic applications. Biomed. Res. Int. 6, 5445291. https://doi.org/10.1155/2022/5445291 (2022). (PMID: 10.1155/2022/5445291)
Frenț, O. D. et al. Systematic review: quercetin-secondary metabolite of the flavonol class, with multiple health benefits and low bioavailability. Int J Mol Sci. 25(22), 12091. (2024). https://doi.org/10.3390/ijms252212091 . PMID: 39596162; PMCID: PMC11594109.
Sanna, V., Pala, N. & Sechi, M. Targeted therapy using nanotechnology: Focus on cancer. Int. J. Nanomed. 9, 467–483. https://doi.org/10.2147/IJN.S46926 (2014). (PMID: 10.2147/IJN.S46926)
Sanna, V., Siddiqui, I. A., Sechi, M. & Mukhtar, H. Resveratrol-loaded nanoparticles based on poly(ε-caprolactone) and poly(d,l-lactic-co-glycolic acid)–poly(ethylene glycol) blend for prostate cancer treatment. Mol. Pharm. 10 (10), 3871–3881. https://doi.org/10.1021/mp4003652 (2015). (PMID: 10.1021/mp4003652)
Jonsson, M. et al. Application of OECD guideline 423 in assessing the acute oral toxicity of moniliformin. Food Chem. Toxicol. 53, 27–32. https://doi.org/10.1016/j.fct.2012.11.023 (2013). (PMID: 10.1016/j.fct.2012.11.02323201451)
Bedi, O. & Krishan, P. Investigations on acute oral toxicity studies of purpurin by application of OECD guideline 423 in rodents. Naunyn Schmiedebergs Arch Pharmacol. 2020;393(4):565–571. (2020). https://doi.org/10.1007/s00210-019-01742-y . Epub 2019 Nov 12. PMID: 31713650.
Harwood, M. et al. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food Chem. Toxicol. 45(11), 2179–2205. https://doi.org/10.1016/j.fct.2007.05.015 (2007).
Aghababaei, F. & Hadidi, M. Recent advances in potential health benefits of Quercetin. Pharmaceuticals (Basel) 16(7), 18. https://doi.org/10.3390/ph16071020 (2023). (PMID: 10.3390/ph16071020)
Liu, J. et al. Quercetin-driven Akkermansia muciniphila alleviates obesity by modulating bile acid metabolism via an ILA/m6A/CYP8B1 signaling. Adv. Sci. 12(12), e2412865. https://doi.org/10.1002/advs.202412865 (2025). (PMID: 10.1002/advs.202412865)
Hong, S. Y., Ha, A. W. & Kim, W. Effects of quercetin on cell differentiation and adipogenesis in 3T3-L1 adipocytes. Nutr. Res. Pract. 15(4), 444–455. https://doi.org/10.4162/nrp.2021.15.4.444 (2021). (PMID: 10.4162/nrp.2021.15.4.444343498788313392)
Maleki, M. H. et al. The effect of quercetin on adipogenesis, lipolysis, and apoptosis in 3T3-L1 adipocytes: The role of SIRT1 pathways. Obes Sci Pract. 2024;10(2):e752. (2024). https://doi.org/10.1002/osp4.752 . PMID: 38618521; PMCID: PMC11015901.
Tabrizi, R. et al. The effects of quercetin supplementation on lipid profiles and inflammatory markers among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials. Crit. Rev. Food Sci. Nutr. 60(11), 1855–1868. https://doi.org/10.1080/10408398.2019.1604491 (2020). (PMID: 10.1080/10408398.2019.160449131017459)
Yi, H. et al. The therapeutic effects and mechanisms of quercetin on metabolic diseases: Pharmacological data and clinical evidence. Oxid. Med. Cell. Longev. 2021, 6678662. https://doi.org/10.1155/2021/6678662 (2021). (PMID: 10.1155/2021/6678662342578178249127)
Pinheiro, R. G. R., Pinheiro, M. & Neves, A. R. Nanotechnology Innovations to Enhance the Therapeutic Efficacy of Quercetin. Nanomaterials (Basel). 2021;11(10):2658. (2021). https://doi.org/10.3390/nano11102658 . PMID: 34685098; PMCID: PMC8539325.
Baiomy, R. F. E. Quercetin nanoparticles as a therapeutic approach: pharmacological actions and potential applications in therapy. BioTechnologia (Pozn). 2024;105(4):377–393. (2024). https://doi.org/10.5114/bta.2024.145258 . PMID: 39844873; PMCID: PMC11748223.
Samantaray, A. et al. Nanoquercetin based nanoformulations for triple negative breast cancer therapy and its role in overcoming drug resistance. Discov Oncol. 2024;15(1):452. (2024). https://doi.org/10.1007/s12672-024-01239-y . PMID: 39287822; PMCID: PMC11408462.
Jin, D. et al. Effects of Quercetin on Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Meta-Analysis. Food Sci Nutr. 2025;13(12):e71358. (2025). https://doi.org/10.1002/fsn3.71358 . PMID: 41404533; PMCID: PMC12703814.
Pingili, R. B. et al. Systematic review on hepatoprotective activity of quercetin against various drugs and toxic agents: Evidence from preclinical studies. Phytother. Res. 34(1), 5–32. https://doi.org/10.1002/ptr.6503 (2025). (PMID: 10.1002/ptr.6503)
Kábelová, A. et al. Quercetin supplementation alters adipose tissue and hepatic transcriptomes and ameliorates adiposity, dyslipidemia, and glucose intolerance in adult male rats. Front. Nutr. 9, 952065. https://doi.org/10.3389/fnut.2022.952065 (2022). (PMID: 10.3389/fnut.2022.952065362454909558266)
Kršková, K. et al. Modification of adipogenesis and oxidative stress by quercetin: positive or negative impact on adipose tissue metabolism of obese diabetic Zucker rats? J Physiol Biochem. 81(1), 137–156. (2025). https://doi.org/10.1007/s13105-024-01060–9 . Epub 2024 Nov 22. PMID: 39576482; PMCID: PMC11958396.
Najafabadi, R. E., Kazemipour, N., Esmaeili, A., Beheshti, S. & Nazifi, S. Quercetin prevents body weight loss due to the using of superparamagnetic iron oxide nanoparticles in rat. Adv. Biomed. Res. 7(1), 8. https://doi.org/10.4103/abr.abr_141_17 (2018).
Hebbard, L. & George, J. Animal models of nonalcoholic fatty liver disease. Nat. Rev. Gastroenterol. Hepatol. 8(1), 35–44. https://doi.org/10.1038/nrgastro.2010.191 (2011). (PMID: 10.1038/nrgastro.2010.19121119613)
Tarantino, G., Citro, V. & Finelli, C. Hype or reality: Should patients with metabolic syndrome-related NAFLD be on the lookout for bone mineral density loss? World J. Gastroenterol. 21 (46), 13235–13244. https://doi.org/10.3748/wjg.v21.i46.13235 (2015). (PMID: 10.3748/wjg.v21.i46.13235)
Donath, M. Y. & Shoelson, S. E. Type 2 diabetes as an inflammatory disease. Nat. Rev. Immunol. 11(2), 98–107. https://doi.org/10.1038/nri2925 (2011). (PMID: 10.1038/nri292521233852)
Lilly, A. C., Astsaturov, I. & Golemis, E. A. Intrapancreatic fat, pancreatitis, and pancreatic cancer. Cell Mol Life Sci. 80(8), 206. (2023). https://doi.org/10.1007/s00018-023-04855-z . PMID: 37452870; PMCID: PMC10349727.
Wang, Y., Li, Z., He, J. & Zhao, Y. Quercetin regulates lipid metabolism and fat accumulation by regulating inflammatory responses and glycometabolism pathways: A review. Nutrients 16(8), 1102. https://doi.org/10.3390/nu16081102 (2024). (PMID: 10.3390/nu160811023867479311053503)
Zhou, M. et al. Bioactivity and mechanisms of flavonoids in decreasing insulin resistance. J. Enzyme Inhib. Med. Chem. 38(1), 2199168. https://doi.org/10.1080/14756366.2023.2199168 (2024). (PMID: 10.1080/14756366.2023.2199168)
Krauss, R. M. et al. AHA dietary guidelines: Revision 2000: A statement for healthcare professionals from the Nutrition Committee of the American Heart Association. Circulation 102(18), 2284–2299. https://doi.org/10.1161/01.CIR.102.18.2284 (2000). (PMID: 10.1161/01.CIR.102.18.228411056107)
National Research Council. Guide for the care and use of laboratory animals (8th ed.). National Academies Press. (2011). https://doi.org/10.17226/12910.
Tomou, E. M. et al. Recent advances in nanoformulations for Quercetin delivery. Pharmaceutics 15(5), 1656. https://doi.org/10.3390/pharmaceutics15061656 (2023). (PMID: 10.3390/pharmaceutics150616563737610410302355)

Keywords: Flavonoids; Hepatic and Pancreatic Function; High-Fat Diet; Lipid Metabolism; Nanoparticles; Oxidative DNA Damage

9IKM0I5T1E (Quercetin)
0 (Adipokines)
0 (Anti-Obesity Agents)
0 (Lipids)

Date Created: 20260322 Date Completed: 20260324 Latest Revision: 20260326

20260329

PMC13009512

10.1038/s41598-026-41808-5

41865024