{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:26:16Z","timestamp":1782282376678,"version":"3.54.5"},"reference-count":108,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T00:00:00Z","timestamp":1645574400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Efeom Nutrition S.A.","award":["01\/04-21"],"award-info":[{"award-number":["01\/04-21"]}]},{"DOI":"10.13039\/501100000828","name":"Royal Society of Medicine","doi-asserted-by":"publisher","award":["2016\/R1 Newton Grant\u2014eGAP SZ50730"],"award-info":[{"award-number":["2016\/R1 Newton Grant\u2014eGAP SZ50730"]}],"id":[{"id":"10.13039\/501100000828","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["#312514\/2019-0"],"award-info":[{"award-number":["#312514\/2019-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>The use of natural products and derivatives for the prevention and control of non-communicable chronic diseases, such as type-2 diabetes (T2D), obesity, and hepatic steatosis is a way to achieve homeostasis through different metabolic pathways. Thus, male C57BL\/6 mice were divided into the following groups: high-fat diet (HFD) vehicle, HFD + Supplemented, HFD + Supplemented_S, and isolated compounds. The vehicle and experimental formulations were administered orally by gavage once a day over the four weeks of the diet (28 consecutive days). We evaluated the energy homeostasis, cytokines, and mitochondrial gene expression in these groups of mice. After four weeks of supplementation, only the new nutraceutical group (HFD + Supplemented) experienced reduced fasting glycemia, insulin, HOMA index, HOMA-\u03b2, dyslipidemia, ectopic fat deposition, and hepatic fibrosis levels. Additionally, the PPAR\u03b3 coactivator 1 \u03b1 (Pgc-1\u03b1), interleukin-6 (Il-6), and interleukin-10 (Il-10) gene expression were augmented, while hepatic steatosis decreased and liver parenchyma was recovered. The glutathione-S-transferase activity status was found to be modulated by the supplement. We discovered that the new nutraceutical was able to improve insulin resistance and hepatic steatosis mainly by regulating IL-6, IL-10, and Pgc-1\u03b1 gene expression.<\/jats:p>","DOI":"10.3390\/antiox11030447","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T22:54:02Z","timestamp":1645656842000},"page":"447","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The Symbiotic Effect of a New Nutraceutical with Yeast \u03b2-Glucan, Prebiotics, Minerals, and Silybum marianum (Silymarin) for Recovering Metabolic Homeostasis via Pgc-1\u03b1, Il-6, and Il-10 Gene Expression in a Type-2 Diabetes Obesity Model"],"prefix":"10.3390","volume":"11","author":[{"given":"Aline Boveto","family":"Santamarina","sequence":"first","affiliation":[{"name":"Department of Biosciences, Federal University of S\u00e3o Paulo (UNIFESP), Santos 11015-020, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0178-8480","authenticated-orcid":false,"given":"Ruan Carlos Mac\u00eado","family":"Moraes","sequence":"additional","affiliation":[{"name":"Natural Products and Derivatives Laboratory (LIM-26), Department of Surgery, University of S\u00e3o Paulo Medical School, S\u00e3o Paulo 01246-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Nehmi Filho","sequence":"additional","affiliation":[{"name":"Natural Products and Derivatives Laboratory (LIM-26), Department of Surgery, University of S\u00e3o Paulo Medical School, S\u00e3o Paulo 01246-903, SP, Brazil"},{"name":"Research and Development Efeom Nutrition S\/A, S\u00e3o Paulo 03317-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilson Masahiro","family":"Murata","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Investigation (LIM-29), Clinic Medical Department, University of S\u00e3o Paulo Medical School, S\u00e3o Paulo 01246-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9457-4587","authenticated-orcid":false,"given":"J\u00e9ssica Alves","family":"de Freitas","sequence":"additional","affiliation":[{"name":"Natural Products and Derivatives Laboratory (LIM-26), Department of Surgery, University of S\u00e3o Paulo Medical School, S\u00e3o Paulo 01246-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle Araujo","family":"de Miranda","sequence":"additional","affiliation":[{"name":"Department of Physiology, Escola Paulista de Medicina\/Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04023-062, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7057-2563","authenticated-orcid":false,"given":"Anderson Rom\u00e9rio Azevedo","family":"Cerqueira","sequence":"additional","affiliation":[{"name":"Departamento de Farmacologia, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2574-4490","authenticated-orcid":false,"given":"Soraia Katia Pereira","family":"Costa","sequence":"additional","affiliation":[{"name":"Departamento de Farmacologia, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Fl\u00e1via Fernandes","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Departamento de Fisiologia, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz Roberto","family":"Britto","sequence":"additional","affiliation":[{"name":"Departamento de Fisiologia, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5624-3798","authenticated-orcid":false,"given":"Juliana Alves","family":"de Camargo","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Investigation (LIM-55), Urology Department, University of S\u00e3o Paulo Medical School, S\u00e3o Paulo 01246-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0579-7234","authenticated-orcid":false,"given":"Daniela","family":"Rodrigues de Oliveira","sequence":"additional","affiliation":[{"name":"Natural Products and Derivatives Laboratory (LIM-26), Department of Surgery, University of S\u00e3o Paulo Medical School, S\u00e3o Paulo 01246-903, SP, Brazil"},{"name":"Genomic Sciences and Precision Medicine Center (GSPMC), Department of Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia Neto","family":"de Jesus","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine Alberta, Calgary, AB T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Pinhata","family":"Otoch","sequence":"additional","affiliation":[{"name":"Natural Products and Derivatives Laboratory (LIM-26), Department of Surgery, University of S\u00e3o Paulo Medical School, S\u00e3o Paulo 01246-903, SP, Brazil"},{"name":"Research and Development Efeom Nutrition S\/A, S\u00e3o Paulo 03317-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Fl\u00e1via Mar\u00e7al","family":"Pessoa","sequence":"additional","affiliation":[{"name":"Natural Products and Derivatives Laboratory (LIM-26), Department of Surgery, University of S\u00e3o Paulo Medical School, S\u00e3o Paulo 01246-903, SP, Brazil"},{"name":"Research and Development Efeom Nutrition S\/A, S\u00e3o Paulo 03317-000, SP, Brazil"},{"name":"Brazilian Academic Consortium for Integrative Health (CABSIN), Natural Products Committee, S\u00e3o Paulo 05449-070, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rosenzweig, T., and Sampson, S.R. (2021). Activation of insulin signaling by botanical products. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22084193"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Konstantinidi, M., and Koutelidakis, A.E. (2019). Functional Foods and Bioactive Compounds: A Review of Its Possible Role on Weight Management and Obesity\u2019s Metabolic Consequences. Medicines, 6.","DOI":"10.3390\/medicines6030094"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/B978-0-12-819483-6.00005-9","article-title":"Bioactive natural products for the prevention and treatment of diabetes mellitus","volume":"Volume 29","author":"Naufel","year":"2020","journal-title":"Studies in Natural Products Chemistry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.intimp.2016.02.005","article-title":"Modulation of Toll-like receptor signaling in innate immunity by natural products","volume":"37","author":"Chen","year":"2016","journal-title":"Int. Immunopharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.joim.2021.05.002","article-title":"A novel supplement with yeast \u03b2-glucan, prebiotic, minerals and Silybum marianum synergistically modulates metabolic and inflammatory pathways and improves steatosis in obese mice","volume":"19","author":"Nehmi","year":"2021","journal-title":"J. Integr. Med."},{"key":"ref_6","first-page":"101","article-title":"A life course approach to diet, nutrition and the prevention of chronic diseases","volume":"7","author":"Nishida","year":"2007","journal-title":"Public Health Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1097\/MCO.0b013e328042ba90","article-title":"Free fatty acids and insulin resistance","volume":"10","author":"Delarue","year":"2007","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1093\/jn\/133.4.1081","article-title":"A controlled high-fat diet induces an obese syndrome in rats","volume":"133","author":"Woods","year":"2003","journal-title":"J. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.lfs.2016.02.002","article-title":"Oxidative stress and metabolic disorders: Pathogenesis and therapeutic strategies","volume":"148","author":"Rani","year":"2016","journal-title":"Life Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1007\/s10787-018-0458-0","article-title":"IL-6 signalling pathways and the development of type 2 diabetes","volume":"26","author":"Akbari","year":"2018","journal-title":"Inflammopharmacology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1172\/JCI29069","article-title":"Inflammation and insulin resistance","volume":"116","author":"Shoelson","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s11684-013-0262-6","article-title":"Mechanisms of insulin resistance in obesity","volume":"7","author":"Ye","year":"2013","journal-title":"Front. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1017\/S0029665113001249","article-title":"Ectopic fat, insulin resistance and non-alcoholic fatty liver disease","volume":"72","author":"Byrne","year":"2013","journal-title":"Proc. Nutr. Soc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1146\/annurev-immunol-031210-101322","article-title":"Inflammatory mechanisms in obesity","volume":"29","author":"Gregor","year":"2011","journal-title":"Annu. Rev. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1079\/BJN2003000968","article-title":"Effect of high-fat feeding on metabolic efficiency and mitochondrial oxidative capacity in adult rats","volume":"90","author":"Iossa","year":"2003","journal-title":"Br. J. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1053\/j.gastro.2011.06.061","article-title":"A Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States","volume":"141","author":"Charlton","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S412","DOI":"10.1194\/jlr.R800089-JLR200","article-title":"Nonalcoholic fatty liver disease","volume":"50","author":"Erickson","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/nyas.12016","article-title":"Nonalcoholic fatty liver disease: An emerging threat to obese and diabetic individuals","volume":"1281","author":"Masuoka","year":"2013","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.2337\/diacare.27.8.2057","article-title":"Approach to the pathogenesis and treatment of nonalcoholic steatohepatitis","volume":"27","author":"Medina","year":"2004","journal-title":"Diabetes Care"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature05485","article-title":"Inflammation and metabolic disorders","volume":"444","author":"Hotamisligil","year":"2006","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"10751","DOI":"10.1096\/fj.201902476R","article-title":"PGC1\u03b1 protects against hepatic steatosis and insulin resistance via enhancing IL10-mediated anti-inflammatory response","volume":"34","author":"Wan","year":"2020","journal-title":"FASEB J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.it.2014.12.008","article-title":"Versatile functions for IL-6 in metabolism and cancer","volume":"36","author":"Mauer","year":"2015","journal-title":"Trends Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.2337\/diabetes.53.4.1060","article-title":"Differential Effects of Interleukin-6 and -10 on Skeletal Muscle and Liver Insulin Action In Vivo","volume":"53","author":"Kim","year":"2004","journal-title":"Diabetes"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3417","DOI":"10.1210\/en.2004-1468","article-title":"Interleukin-6 depletion selectively improves hepatic insulin action in obesity","volume":"146","author":"Klover","year":"2005","journal-title":"Endocrinology"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Cena, H., and Calder, P.C. (2020). Defining a healthy diet: Evidence for the role of contemporary dietary patterns in health and disease. Nutrients, 12.","DOI":"10.3390\/nu12020334"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.pharmthera.2011.01.012","article-title":"The gut microbiome as therapeutic target","volume":"130","author":"Cani","year":"2011","journal-title":"Pharmacol. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/BF03180584","article-title":"Dietary fructooligosaccharides and potential benefits on health","volume":"65","author":"Torrella","year":"2009","journal-title":"J. Physiol. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1111\/j.1541-4337.2010.00119.x","article-title":"Galacto-Oligosaccharides: Production, properties, applications, and significance as prebiotics","volume":"9","author":"Torres","year":"2010","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Andrade, E.F., Lima, A.R.V., Nunes, I.E., Orlando, D.R., Gondim, P.N., Zangeronimo, M.G., Alves, F.H.F., and Pereira, L.J. (2016). Exercise and beta-glucan consumption (Saccharomyces cerevisiae) improve the metabolic profile and reduce the atherogenic index in type 2 diabetic rats (HFD\/STZ). Nutrients, 8.","DOI":"10.3390\/nu8120792"},{"key":"ref_30","first-page":"256","article-title":"Metabolic effects of \u03b2-glucans (Saccharomyces cerevisae) per os administration in rats with streptozotocin-induced diabetes","volume":"32","author":"Lobato","year":"2015","journal-title":"Nutr. Hosp."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1111\/j.1753-4887.2010.00293.x","article-title":"Magnesium, inflammation, and obesity in chronic disease","volume":"68","author":"Nielsen","year":"2010","journal-title":"Nutr. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s12011-013-9885-3","article-title":"Effect of zinc supplementation on inflammatory markers and adipokines in young obese women","volume":"157","author":"Kim","year":"2014","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1016\/S0140-6736(11)61452-9","article-title":"Selenium and human health","volume":"379","author":"Rayman","year":"2012","journal-title":"Lancet"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1002\/ptr.6171","article-title":"Milk thistle (Silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases","volume":"32","author":"Izzo","year":"2018","journal-title":"Phytother. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S215","DOI":"10.2337\/diabetes.53.suppl_3.S215","article-title":"The High-Fat Diet-Fed Mouse: A Model for Studying Mechanisms and Treatment of Impaired Glucose Tolerance and Type 2 Diabetes","volume":"53","author":"Winzell","year":"2004","journal-title":"Diabetes"},{"key":"ref_36","unstructured":"(2017). Dietary Reference Values for nutrients Summary report. EFSA Support. Publ., 14, e15121."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1053\/j.gastro.2017.03.051","article-title":"in Obese Prediabetic Individuals","volume":"153","author":"Canfora","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1097\/MCG.0000000000000328","article-title":"Effects of Prebiotic and Synbiotic Supplementation on Inflammatory Markers and Anthropometric Indices After Roux-en-Y Gastric Bypass","volume":"50","author":"Randomized","year":"2016","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/mnfr.201300338","article-title":"Effects of orally administered yeast-derived beta-glucans: A review","volume":"58","author":"Samuelsen","year":"2014","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A simple practice guide for dose conversion between animals and human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic Clin. Pharm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.joim.2020.03.001","article-title":"Guidelines for diagnosis and treatment of hepatic fibrosis with integrated traditional Chinese and Western medicine (2019 edition)","volume":"18","author":"Xu","year":"2020","journal-title":"J. Integr. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.jnutbio.2018.07.009","article-title":"Liraglutide modulates gut microbiota and reduces NAFLD in obese mice","volume":"62","author":"Moreira","year":"2018","journal-title":"J. Nutr. Biochem."},{"key":"ref_43","first-page":"2017","article-title":"Intermittent cafeteria diet identi fi es fecal microbiome changes as a predictor of spatial recognition memory impairment in female rats","volume":"43","author":"Leigh","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1093\/clinchem\/18.6.499","article-title":"Estimation of the Concentration of Low-Density Lipoprotein Cholesterol in Plasma,Without Use of the Preparative Ultracentrifuge","volume":"18","author":"Friedewald","year":"1972","journal-title":"Clin. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: Insulin resistance and \u03b2-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"De O. Silva, V., Lobato, R., Andrade, E., Orlando, D., Borges, B., Zangeronimo, M., de Sousa, R., and Pereira, L. (2017). Effects of \u03b2-Glucans Ingestion on Alveolar Bone Loss, Intestinal Morphology, Systemic Inflammatory Profile, and Pancreatic \u03b2-Cell Function in Rats with Periodontitis and Diabetes. Nutrients, 9.","DOI":"10.3390\/nu9091016"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1038\/nprot.2013.055","article-title":"Imaging of neutral lipids by oil red O for analyzing the metabolic status in health and disease","volume":"8","author":"Mehlem","year":"2013","journal-title":"Nat. Protoc."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4986","DOI":"10.1101\/pdb.prot4986","article-title":"Hematoxylin and eosin staining of tissueand cell sections","volume":"3","author":"Fischer","year":"2008","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_49","first-page":"3946","article-title":"Selection of reference genes for expression analyses in liver of rats with impaired glucose metabolism","volume":"8","author":"Curi","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1111\/j.1469-185X.2007.00027.x","article-title":"Effect size, confidence interval and statistical significance: A practical guide for biologists","volume":"82","author":"Nakagawa","year":"2007","journal-title":"Biol. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3102\/10769986006002107","article-title":"Distribution Theory for Glass \u2019 s Estimator of Effect Size and Related Estimators","volume":"6","author":"Hedges","year":"2014","journal-title":"J. Educ. Stat."},{"key":"ref_53","first-page":"587","article-title":"Mechanism linking diabetes mellitus and obesity","volume":"7","author":"Khan","year":"2014","journal-title":"Diabetes Metab. Syndr. Obes. Targets Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1210\/er.2001-0039","article-title":"Oxidative stress and stress-activated signaling pathways: A unifying hypothesis of type 2 diabetes","volume":"23","author":"Evans","year":"2002","journal-title":"Endocr. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"6797460","DOI":"10.1155\/2017\/6797460","article-title":"The Involvement of Mg 2+ in Regulation of Cellular and Mitochondrial Functions","volume":"2017","author":"Pilchova","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1210\/endo-103-4-1440","article-title":"The effect of zinc on insulin metabolism","volume":"103","author":"Arquilla","year":"1978","journal-title":"Endocrinology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1590\/s2175-97902018000100139","article-title":"The role of selenium in insulin resistance","volume":"54","author":"Fontenelle","year":"2018","journal-title":"Braz. J. Pharm. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"100255","DOI":"10.1016\/j.aohep.2020.08.072","article-title":"Silymarin is an ally against insulin resistance: A review","volume":"23","year":"2021","journal-title":"Ann. Hepatol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2678","DOI":"10.1002\/mnfr.201600032","article-title":"Hypoglycemic activity of the Baker\u2019s yeast \u03b2-glucan in obese\/type 2 diabetic mice and the underlying mechanism","volume":"60","author":"Cao","year":"2016","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1590\/S0102-86502012000300013","article-title":"Fructo-oligosaccharide effects on blood glucose. An overview","volume":"27","author":"Costa","year":"2012","journal-title":"Acta Cir. Bras."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s12602-016-9206-1","article-title":"Effect of Prebiotic Galacto-Oligosaccharides on Serum Lipid Profile of Hypercholesterolemics","volume":"8","author":"Hashmi","year":"2016","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Zhu, D., Yan, Q., Li, Y., Liu, J., Liu, H., and Jiang, Z. (2019). Effect of Konjac Mannan oligosaccharides on glucose homeostasis via the improvement of insulin and leptin resistance in vitro and in vivo. Nutrients, 11.","DOI":"10.3390\/nu11081705"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.cell.2013.12.016","article-title":"Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits","volume":"156","author":"Goncalves","year":"2014","journal-title":"Cell"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Reynolds, A.N., Akerman, A.P., and Mann, J. (2020). Dietary fibre and whole grains in diabetes management: Systematic review and meta-analyses. PLoS Med., 17.","DOI":"10.1371\/journal.pmed.1003053"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"11789","DOI":"10.1038\/s41598-017-10722-2","article-title":"Fructooligosaccharide (FOS) and Galactooligosaccharide (GOS) Increase Bifidobacterium but Reduce Butyrate Producing Bacteria with Adverse Glycemic Metabolism in healthy young population","volume":"7","author":"Liu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"9236","DOI":"10.1038\/s41598-020-65936-8","article-title":"Integrative phenotyping of glycemic responders upon clinical weight loss using multi-omics","volume":"10","author":"Valsesia","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/S0140-6736(17)33102-1","article-title":"Primary care-led weight management for remission of type 2 diabetes (DiRECT): An open-label, cluster-randomised trial","volume":"391","author":"Lean","year":"2018","journal-title":"Lancet"},{"key":"ref_68","first-page":"134","article-title":"Physiological changes due to hepatotoxicity and the protective role of some medicinal plants","volume":"5","year":"2016","journal-title":"Beni-Suef Univ. J. Basic Appl. Sci."},{"key":"ref_69","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":"Medecine"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1590\/S1676-24442005000400004","article-title":"Indice HOMA(homeostasis modela assessment) na pratica cl\u00ednica: Uma revis\u00e3o","volume":"41","author":"Oliveira","year":"2005","journal-title":"J. Bras. Patol. E Med. Lab."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1046\/j.1464-5491.2003.00889.x","article-title":"Improvements in insulin sensitivity and \u03b2-cell function (HOMA) with weight loss in the severely obese","volume":"20","author":"Dixon","year":"2003","journal-title":"Diabet. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.freeradbiomed.2010.12.005","article-title":"Oxidative stress and the etiology of insulin resistance and type 2 diabetes","volume":"51","author":"Henriksen","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1002\/oby.21654","article-title":"Reactive Oxygen Species and Oxidative Stress in Obesity\u2014Recent Findings and Empirical Approaches","volume":"24","author":"McMurray","year":"2016","journal-title":"Obesity"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1089\/met.2015.0095","article-title":"Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies","volume":"13","author":"Manna","year":"2015","journal-title":"Metab. Syndr. Relat. Disord."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1124\/dmd.110.035006","article-title":"Diversity in antioxidant response enzymes in progressive stages of human nonalcoholic fatty liver disease","volume":"38","author":"Hardwick","year":"2010","journal-title":"Drug Metab. Dispos."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1007\/s00424-018-2195-z","article-title":"Catalase and nonalcoholic fatty liver disease","volume":"470","author":"Shin","year":"2018","journal-title":"Pflug. Arch. Eur. J. Physiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1111\/j.1478-3231.2005.01126.x","article-title":"Increase in liver antioxidant enzyme activities in non-alcoholic fatty liver disease","volume":"25","author":"Perlemuter","year":"2005","journal-title":"Liver Int."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.freeradbiomed.2016.02.028","article-title":"The role of glutathione reductase and related enzymes on cellular redox homoeostasis network","volume":"95","author":"Couto","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1146\/annurev.pharmtox.45.120403.095857","article-title":"Glutathione transferases","volume":"45","author":"Hayes","year":"2005","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"E1005","DOI":"10.1152\/ajpendo.00345.2017","article-title":"Glutathione s-transferase p deficiency induces glucose intolerance via jnk-dependent enhancement of hepatic gluconeogenesis","volume":"315","author":"Dastidar","year":"2018","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"17787","DOI":"10.1073\/pnas.0902380106","article-title":"Insulin resistance is a cellular antioxidant defense mechanism","volume":"106","author":"Hoehn","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Vairetti, M., Di Pasqua, L.G., Cagna, M., Richelmi, P., Ferrigno, A., and Berardo, C. (2021). Changes in glutathione content in liver diseases: An update. Antioxidants, 10.","DOI":"10.3390\/antiox10030364"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1101\/gad.1138104","article-title":"Peroxisome proliferator-activated receptor-\u03b3 coactivator 1\u03b1 (PGC-1\u03b1) regulates triglyceride metabolism by activation of the nuclear receptor FXR","volume":"18","author":"Zhang","year":"2004","journal-title":"Genes Dev."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/nature05767","article-title":"Transcriptional coactivator PGC-1\u03b1 integrates the mammalian clock and energy metabolism","volume":"447","author":"Liu","year":"2007","journal-title":"Nature"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Kobayashi, M., Deguchi, Y., Nozaki, Y., and Higami, Y. (2021). Contribution of pgc-1\u03b1 to obesity- and caloric restriction-related physiological changes in white adipose tissue. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22116025"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1038\/nm1044","article-title":"PGC-1 promotes insulin resistance in liver through PPAR-\u03b1-dependent induction of TRB-3","volume":"10","author":"Koo","year":"2004","journal-title":"Nat. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1053\/j.gastro.2016.09.017","article-title":"Estrogen Signals Through Peroxisome Proliferator-Activated Receptor\u2212\u03b3 Coactivator 1\u03b1 to Reduce Oxidative Damage Associated With Diet-Induced Fatty Liver Disease","volume":"152","author":"Oropeza","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/s41575-018-0089-3","article-title":"Metabolic aspects in NAFLD, NASH and hepatocellular carcinoma: The role of PGC1 coactivators","volume":"16","author":"Piccinin","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1146\/annurev.med.53.082901.104018","article-title":"The mechanisms of PPARs","volume":"53","author":"Berger","year":"2002","journal-title":"Annu. Rev. Med."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Longo, M., Zatterale, F., Naderi, J., Parrillo, L., Formisano, P., Raciti, G.A., Beguinot, F., and Miele, C. (2019). Adipose tissue dysfunction as determinant of obesity-associated metabolic complications. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092358"},{"key":"ref_91","first-page":"304","article-title":"Adipokines, diabetes and atherosclerosis: An inflammatory association","volume":"6","year":"2015","journal-title":"Front. Physiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1111\/j.1463-1326.2005.00510.x","article-title":"Adiponectin\u2014A key adipokine in the metabolic syndrome","volume":"8","author":"Whitehead","year":"2006","journal-title":"Diabetes Obes. Metab."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Santamarina, A.B., Oliveira, J.L., Silva, F.P., Carnier, J., Mennitti, L.V., Santana, A.A., de Souza, G.H.I., Ribeiro, E.B., Oller do Nascimento, C.M., and Lira, F.S. (2015). Green Tea Extract Rich in Epigallocatechin-3-Gallate Prevents Fatty Liver by AMPK Activation via LKB1 in Mice Fed a High-Fat Diet. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0141227"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"a016295","DOI":"10.1101\/cshperspect.a016295","article-title":"IL-6 in Inflammation, Immunity, and Disease","volume":"6","author":"Tanaka","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Kern, L., Mittenb\u00fchler, M.J., Vesting, A.J., Ostermann, A.L., Wunderlich, C.M., and Wunderlich, F.T. (2019). Obesity-induced TNF\u03b1 and IL-6 signaling: The missing link between obesity and inflammation- driven liver and colorectal cancers. Cancers, 11.","DOI":"10.3390\/cancers11010024"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/S0083-6729(08)00621-3","article-title":"Chapter 21 Interleukin-6 and Insulin Resistance","volume":"80","author":"Kim","year":"2009","journal-title":"Vitam. Horm."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1126\/science.1160794","article-title":"A stress signaling pathway in adipose tissue regulates hepatic insulin resistance","volume":"322","author":"Sabio","year":"2008","journal-title":"Science"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.cmet.2011.02.010","article-title":"Adiponectin enhances insulin sensitivity by increasing hepatic IRS-2 expression via a macrophage-derived IL-6-dependent pathway","volume":"13","author":"Awazawa","year":"2011","journal-title":"Cell Metab."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4285","DOI":"10.1073\/pnas.1815150116","article-title":"PGC1A regulates the IRS1:IRS2 ratio during fasting to influence hepatic metabolism downstream of insulin","volume":"116","author":"Jeromson","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1007\/s00125-010-1865-y","article-title":"Interleukin-6-deficient mice develop hepatic inflammation and systemic insulin resistance","volume":"53","author":"Matthews","year":"2010","journal-title":"Diabetologia"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"14803","DOI":"10.1038\/ncomms14803","article-title":"Temporal and tissue-specific requirements for T-lymphocyte IL-6 signalling in obesity-associated inflammation and insulin resistance","volume":"8","author":"Xu","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s12016-015-8514-7","article-title":"Regulator Versus Effector Paradigm: Interleukin-10 as Indicator of the Switching Response","volume":"50","author":"Mingomataj","year":"2016","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"21244","DOI":"10.1038\/srep21244","article-title":"Hyporesponsiveness to the anti-inflammatory action of interleukin-10 in type 2 diabetes","volume":"6","author":"Barry","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"5876","DOI":"10.1210\/jc.2005-0281","article-title":"Association between circulating adiponectin and interleukin-10 levels in android obesity: Effects of weight loss","volume":"90","author":"Manigrasso","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1038\/mt.2013.125","article-title":"Hydrodynamic delivery of mIL10 gene protects mice from high-fat diet-induced obesity and glucose intolerance","volume":"21","author":"Gao","year":"2013","journal-title":"Mol. Ther."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1371\/journal.pbio.1000465","article-title":"IL-6 and IL-10 anti-inflammatory activity links exercise to hypothalamic insulin and leptin sensitivity through IKK\u03b2 and ER stress inhibition","volume":"8","author":"Ropelle","year":"2010","journal-title":"PLoS Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1152\/japplphysiol.00164.2004","article-title":"The anti-inflammatory effect of exercise","volume":"98","author":"Petersen","year":"2005","journal-title":"J. Appl. Physiol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1152\/ajpendo.00074.2003","article-title":"IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans","volume":"285","author":"Steensberg","year":"2003","journal-title":"Am. J. Physiol. Endocrinol. Metab."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/3\/447\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:25:42Z","timestamp":1760135142000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/3\/447"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,23]]},"references-count":108,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["antiox11030447"],"URL":"https:\/\/doi.org\/10.3390\/antiox11030447","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,23]]}}}