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This study aimed to investigate the therapeutic ability of extract enriched by interruptins A and B (EEI) from an edible fern Cyclosorus terminans on insulin resistance and non-alcoholic fatty liver disease (NAFLD) in a high-fat diet (HFD)-induced obese rats and elucidate their possible mechanisms. HFD-induced obese rats were treated with EEI for 2 weeks. Real-time polymerase chain reaction (PCR) was used to examine the molecular basis. We found that EEI supplementation significantly attenuated body and liver weight gain, glucose intolerance, and insulin resistance. Concurrently, EEI increased liver and soleus muscle glycogen storage and serum high-density lipoprotein (HDL) levels. EEI also attenuated NAFLD, as indicated by improving liver function. These effects were associated with enhanced expression of insulin signaling genes (Slc2a2, Slc2a4, Irs1 and Irs2) along with diminished expression of inflammatory genes (Il6 and Tnf). Furthermore, EEI led to the suppression of lipogenesis genes, Srebf1 and Fasn, together with an increase in fatty acid oxidation genes, Ppara and Cpt2, in the liver. These findings suggest that EEI could ameliorate HFD-induced insulin resistance and NAFLD via improving insulin signaling pathways, inflammatory response, lipogenesis, and fatty acid oxidation.<\/jats:p>","DOI":"10.3390\/nu14224895","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T04:13:36Z","timestamp":1669004016000},"page":"4895","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Cyclosorus terminans Extract Ameliorates Insulin Resistance and Non-Alcoholic Fatty Liver Disease (NAFLD) in High-Fat Diet (HFD)-Induced Obese Rats"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4215-1053","authenticated-orcid":false,"given":"Sujinda","family":"Songtrai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wasana","family":"Pratchayasakul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Busarin","family":"Arunsak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Titikorn","family":"Chunchai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aphisek","family":"Kongkaew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nipon","family":"Chattipakorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1677-7052","authenticated-orcid":false,"given":"Siriporn","family":"Chattipakorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7953-3712","authenticated-orcid":false,"given":"Sireewan","family":"Kaewsuwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107843","DOI":"10.1016\/j.diabres.2019.107843","article-title":"Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition","volume":"157","author":"Saeedi","year":"2019","journal-title":"Diabetes Res. 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