{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T07:28:35Z","timestamp":1777102115020,"version":"3.51.4"},"reference-count":38,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,12]],"date-time":"2023-07-12T00:00:00Z","timestamp":1689120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Center, Poland","doi-asserted-by":"publisher","award":["UMO-2018\/31\/D\/NZ9\/02196"],"award-info":[{"award-number":["UMO-2018\/31\/D\/NZ9\/02196"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Previous studies suggested that dietary supplementation with prebiotic fructooligosaccharides (FOSs) and polyphenols could mitigate disorders related to the first stage of nonalcoholic fatty liver disease (NAFLD) induced by an obesogenic diet. Therefore, this experiment aimed to address whether the health-promoting potential of raspberry polyphenols together with FOSs can regulate advanced-stage NAFLD in Zucker rats genetically predisposed to develop obesity. The addition of FOSs and raspberry polyphenolic extract to the diet reduced liver fat accumulation and triglyceride, free fatty acid, and total cholesterol levels in the liver. The elevated GSH\/GSSG ratio and reduced malondialdehyde content indicated that the liver antioxidant potential was considerably increased. The treatment also lowered the plasma aminotransferase and alkaline phosphatase activities and collagen type IV levels. Insulin levels were decreased, but glucose levels remained constant, indicating greater insulin sensitivity. These changes may result from the upregulation of FXR and AHR receptors in the liver, which are responsible for regulating lipid metabolism and glucose and bile acid synthesis. The reduced bile acid levels in the cecal contents confirmed the activation of liver mechanisms. In conclusion, dietary enrichment with FOSs and raspberry polyphenolic extract has sufficient health-promoting potential to regulate liver metabolism, oxidative stress, and inflammation related to NAFLD development in obese Zucker rats.<\/jats:p>","DOI":"10.3390\/nu15143115","type":"journal-article","created":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T01:52:25Z","timestamp":1689213145000},"page":"3115","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Prebiotics Together with Raspberry Polyphenolic Extract Mitigate the Development of Nonalcoholic Fatty Liver Diseases in Zucker Rats"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9727-7481","authenticated-orcid":false,"given":"Bartosz","family":"Fotschki","sequence":"first","affiliation":[{"name":"Division of Food Science, Institute of Animal Reproduction and Food Research, Tuwima 10, 10-748 Olsztyn, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0848-7629","authenticated-orcid":false,"given":"Micha\u0142","family":"S\u00f3jka","sequence":"additional","affiliation":[{"name":"Institute of Food Technology and Analysis, \u0141\u00f3d\u017a University of Technology, Stefanowskiego 4\/10, 90-924 \u0141\u00f3d\u017a, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9018-3028","authenticated-orcid":false,"given":"Monika","family":"Kosmala","sequence":"additional","affiliation":[{"name":"Institute of Food Technology and Analysis, \u0141\u00f3d\u017a University of Technology, Stefanowskiego 4\/10, 90-924 \u0141\u00f3d\u017a, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0068-5970","authenticated-orcid":false,"given":"Jerzy","family":"Ju\u015bkiewicz","sequence":"additional","affiliation":[{"name":"Division of Food Science, Institute of Animal Reproduction and Food Research, Tuwima 10, 10-748 Olsztyn, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,12]]},"reference":[{"key":"ref_1","unstructured":"(2022). WHO European Regional Obesity Report 2022, WHO Regional Office for Europe. Available online: https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/353747\/9789289057738-eng.pdf."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/s41576-021-00414-z","article-title":"The genetics of obesity: From discovery to biology","volume":"23","author":"Loos","year":"2022","journal-title":"Nat. Rev. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/hep.20734","article-title":"Prevalence of and risk factors for nonalcoholic fatty liver disease: The Dionysos nutrition and liver study","volume":"42","author":"Bedogni","year":"2005","journal-title":"Hepatology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1111\/j.1478-3231.2006.01311.x","article-title":"Prevalence of primary non-alcoholic fatty liver disease in a population-based study and its association with biochemical and anthropometric measures","volume":"26","author":"Halpern","year":"2006","journal-title":"Liver Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.metabol.2015.12.012","article-title":"The Multiple-Hit Pathogenesis of Non-Alcoholic Fatty Liver Disease (NAFLD)","volume":"65","author":"Buzzetti","year":"2016","journal-title":"Metabolism"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.freeradbiomed.2011.10.003","article-title":"Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis","volume":"52","author":"Rolo","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.atherosclerosis.2015.01.001","article-title":"A concise review of non-alcoholic fatty liver disease","volume":"239","author":"Than","year":"2015","journal-title":"Atherosclerosis"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Fotschki, B., Ju\u015bkiewicz, J., Jurgo\u0144ski, A., and S\u00f3jka, M. (2021). Fructo-Oligosaccharides and Pectins Enhance Beneficial Effects of Raspberry Polyphenols in Rats with Nonalcoholic Fatty Liver. Nutrients, 13.","DOI":"10.3390\/nu13030833"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1016\/j.cmet.2021.06.012","article-title":"FXR Activation Protects against NAFLD via Bile-Acid-Dependent Reductions in Lipid Absorption","volume":"33","author":"Clifford","year":"2021","journal-title":"Cell Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"544","DOI":"10.3389\/fmed.2020.00544","article-title":"Bile Acids and FXR: Novel Targets for Liver Diseases","volume":"7","author":"Stofan","year":"2020","journal-title":"Front. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1002\/hep.21655","article-title":"Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis","volume":"45","author":"Yamaguchi","year":"2007","journal-title":"Hepatology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.jhepr.2019.07.002","article-title":"From NASH to Diabetes and from Diabetes to NASH: Mechanisms and Treatment Options","volume":"1","author":"Gastaldelli","year":"2019","journal-title":"JHEP Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1039\/C7FO00893G","article-title":"An exploratory study of red raspberry (Rubus idaeus L.) (poly)phenols\/metabolites in human biological samples","volume":"21","author":"Zhang","year":"2018","journal-title":"Food Funct."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2926","DOI":"10.1021\/jf0111209","article-title":"Antioxidant and antiproliferative activities of raspberries","volume":"50","author":"Liu","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Fotschki, B., Laparra, J., and S\u00f3jka, M. (2018). Raspberry Polyphenolic Extract Regulates Obesogenic Signals in Hepatocytes. Molecules, 23.","DOI":"10.3390\/molecules23092103"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"111754","DOI":"10.1016\/j.foodres.2022.111754","article-title":"Stimulation of the Intestinal Microbiota with Prebiotics Enhances Hepatic Levels of Dietary Polyphenolic Compounds, Lipid Metabolism and Antioxidant Status in Healthy Rats","volume":"160","author":"Fotschki","year":"2022","journal-title":"Food Res. Int."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Klewicka, E., S\u00f3jka, M., Klewicki, R., Ko\u0142odziejczyk, K., Lipi\u0144ska, L., and Nowak, A. (2016). Ellagitannins from raspberry (Rubus idaeus L.) fruit as natural inhibitors of Geotrichum candidum. Molecules, 21.","DOI":"10.3390\/molecules21070908"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1007\/s00217-013-2070-2","article-title":"Nutrient and polyphenolic composition of industrial strawberry press cake","volume":"237","author":"Klimczak","year":"2013","journal-title":"Eur. Food Res. Technol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Fotschki, B., Cholewi\u0144ska, E., Ognik, K., S\u00f3jka, M., Milala, J., Fotschki, J., Wiczkowski, W., and Ju\u015bkiewicz, J. (2023). Dose-Related Regulatory Effect of Raspberry Polyphenolic Extract on Cecal Microbiota Activity, Lipid Metabolism and Inflammation in Rats Fed a Diet Rich in Saturated Fats. Nutrients, 15.","DOI":"10.3390\/nu15020354"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3159","DOI":"10.1038\/nprot.2006.378","article-title":"Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling method","volume":"1","author":"Rahman","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1021\/jf00045a019","article-title":"Rapid, sensitive, and specific thiobarbituric acid method for measuring lipid peroxidation in animal tissue, food, and feedstuff samples","volume":"42","author":"Botsoglou","year":"1994","journal-title":"J. Agric. Food Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0021-9258(18)64849-5","article-title":"A simple method for the isolation and purification of total lipids from animal tissues","volume":"226","author":"Folch","year":"1957","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.matbio.2011.04.004","article-title":"Scarless skin wound healing in FOXN1 deficient (nude) mice is associated with distinctive matrix metalloproteinase expression","volume":"30","year":"2011","journal-title":"Matrix Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1007\/s10620-009-0815-3","article-title":"Characterization of high-fat, diet-induced, non-alcoholic steatohepatitis with fibrosis in rats","volume":"55","author":"Xu","year":"2010","journal-title":"Dig. Dis. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1111\/j.1572-0241.1999.01377.x","article-title":"Nonalcoholic steatohepatitis: A proposal for grading and staging the histological lesions","volume":"94","author":"Brunt","year":"1999","journal-title":"Am. J. Gastroenterol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3748\/wjg.v25.i2.163","article-title":"Current status, problems, and perspectives of non-alcoholic fatty liver disease research","volume":"25","author":"Tanaka","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8364","DOI":"10.3748\/wjg.v20.i26.8364","article-title":"Experimental models of non-alcoholic fatty liver disease in rats","volume":"20","author":"Kucera","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"113127","DOI":"10.1016\/j.biopha.2022.113127","article-title":"Natural PPARs agonists for the treatment of nonalcoholic fatty liver disease","volume":"151","author":"Pan","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1093\/cdn\/nzaa045_085","article-title":"Raspberry Polyphenol Extracts Modify Physiological Parameters and the Hepatic Transcriptome of C57BL\/6J Mice Fed a High-Fat Diet","volume":"4","author":"Pierce","year":"2020","journal-title":"Curr. Dev. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Takai, A., Kikuchi, K., Ichimura, M., Tsuneyama, K., Moritoki, Y., Matsumoto, K., Tsunashima, H., Onda, T., Kuniyoshi, N., and Nariyama, T. (2020). Fructo-oligosaccharides ameliorate steatohepatitis, visceral adiposity, and associated chronic inflammation via increased production of short-chain fatty acids in a mouse model of non-alcoholic steatohepatitis. BMC Gastroenterol., 20.","DOI":"10.1186\/s12876-020-01194-2"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"100253","DOI":"10.1016\/j.aohep.2020.08.070","article-title":"Usefulness of Collagen Type IV in the Detection of Significant Liver Fibrosis in Nonalcoholic Fatty Liver Disease","volume":"20","author":"Stefano","year":"2021","journal-title":"Ann. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/s41574-019-0266-7","article-title":"Bile acids in glucose metabolism and insulin signalling\u2014Mechanisms and research needs","volume":"15","author":"Ahmad","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e26835","DOI":"10.1097\/MD.0000000000026835","article-title":"Decline in Serum Albumin Concentration Is a Predictor of Serious Events in Nonalcoholic Fatty Liver Disease","volume":"100","author":"Kawaguchi","year":"2021","journal-title":"Medicine"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1007\/s12072-015-9665-6","article-title":"Albumin in Chronic Liver Disease: Structure, Functions and Therapeutic Implications","volume":"10","author":"Spinella","year":"2015","journal-title":"Hepatol. Int."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Anderson, K.M., and Gayer, C.P. (2021). The Pathophysiology of Farnesoid X Receptor (FXR) in the GI Tract: Inflammation, Barrier Function and Innate Immunity. Cells, 10.","DOI":"10.3390\/cells10113206"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1039\/C6FO01810F","article-title":"Mechanisms and Therapeutic Prospects of Polyphenols as Modulators of the Aryl Hydrocarbon Receptor","volume":"8","author":"Xue","year":"2017","journal-title":"Food Funct."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.toxlet.2019.10.010","article-title":"In Vitro and in Vivo Approaches for Identifying the Role of Aryl Hydrocarbon Receptor in the Development of Nonalcoholic Fatty Liver Disease","volume":"319","author":"Zhu","year":"2020","journal-title":"Toxicol. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Grishanova, A.Y., and Perepechaeva, M.L. (2022). Aryl Hydrocarbon Receptor in Oxidative Stress as a Double Agent and Its Biological and Therapeutic Significance. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23126719"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/14\/3115\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:11:27Z","timestamp":1760127087000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/14\/3115"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,12]]},"references-count":38,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["nu15143115"],"URL":"https:\/\/doi.org\/10.3390\/nu15143115","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,12]]}}}