{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T23:29:30Z","timestamp":1785540570250,"version":"3.56.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:p>The marine microalga <jats:italic>Nannochloropsis gaditana<\/jats:italic> is a fast-growing species rich in long-chain polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA), and other bioactive compounds. In this study, lipids from <jats:italic>N. gaditana<\/jats:italic> powder were extracted and refined using subcritical butane combined with molecular distillation to obtain a highly purified lipid extract with increased EPA concentration (58.92% w\/w) and improved biological activity. The anti-hyperlipidemic effects of the lipid extract were evaluated in female Kunming mice (4 weeks old) fed a high-fat diet. Results demonstrated that <jats:italic>N. gaditana<\/jats:italic> lipid supplementation significantly reduced body weight gain, serum triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C), while elevating high-density lipoprotein cholesterol (HDL-C). Additionally, the lipid extract ameliorated hepatic inflammation (reduced TNF-\u03b1 and IL-1\u03b2 levels), attenuated oxidative stress (enhanced SOD, CAT, and GSH-Px activities), and modulated lipid metabolism enzymes (inhibited FAS, ACC, and HMGCR; upregulated LCAT). These findings highlight the potential of EPA-rich <jats:italic>N. gaditana<\/jats:italic> lipid as a natural and sustainable therapeutic strategy for managing hyperlipidemia and associated metabolic disorders.<\/jats:p>","DOI":"10.3389\/fnut.2025.1615332","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T04:10:17Z","timestamp":1750911017000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Subcritical fluid and molecular distillation extraction of Nannochloropsis gaditana lipid and its metabolic benefits in hyperlipidemic mice"],"prefix":"10.3389","volume":"12","author":[{"given":"Ruilong","family":"Meng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yishan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongliang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,26]]},"reference":[{"key":"B1","year":"2020","journal-title":"Global Health Estimates 2020: Deaths by Cause, Age, Sex, by Country and Region, 2000\u20132019."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2889","DOI":"10.1016\/j.jacc.2013.11.002","article-title":"2013 ACC\/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of the American College of Cardiology\/American Heart Association task force on practice guidelines.","volume":"63","author":"Stone","year":"2014","journal-title":"J Am Coll Cardiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1042\/BST20160474","article-title":"Omega-3 fatty acids and inflammatory processes: From molecules to man.","volume":"45","author":"Calder","year":"2017","journal-title":"Biochem Soc Trans."},{"key":"B4","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.aquaculture.2015.01.010","article-title":"Omega-3 long-chain polyunsaturated fatty acids and aquaculture in perspective.","volume":"449","author":"Tocher","year":"2015","journal-title":"Aquacult."},{"key":"B5","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/j.biotechadv.2007.02.001","article-title":"Biodiesel from microalgae.","volume":"25","author":"Chisti","year":"2007","journal-title":"Biotechnol Adv."},{"key":"B6","doi-asserted-by":"publisher","first-page":"128","DOI":"10.3390\/md23030128","article-title":"Nannochloropsis lipids and polyunsaturated fatty acids: Potential applications and strain improvement.","volume":"23","author":"Navalho","year":"2025","journal-title":"Mar Drugs."},{"key":"B7","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1002\/bit.22033","article-title":"Microalgae for oil: Strain selection, induction of lipid synthesis and outdoor mass cultivation in a low-cost photobioreactor.","volume":"102","author":"Rodolfi","year":"2009","journal-title":"Biotechnol Bioeng."},{"key":"B8","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1016\/j.biotechadv.2012.01.001","article-title":"Extraction of oil from microalgae for biodiesel production: A review.","volume":"30","author":"Halim","year":"2012","journal-title":"Biotechnol Adv."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1854","DOI":"10.3390\/molecules23081854","article-title":"Supercritical CO2 extraction of nannochloropsis sp.: A lipidomic study on the influence of pretreatment on yield and composition.","volume":"23","author":"Elst","year":"2018","journal-title":"Molecules."},{"key":"B10","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1016\/j.supflu.2008.10.008","article-title":"The extraction and fractionation of specialty lipids using near critical fluids.","volume":"47","author":"Catchpole","year":"2009","journal-title":"J. Supercrit. Fluids."},{"key":"B11","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1002\/jsfa.9258","article-title":"Highly concentrated omega-3 fatty acid ethyl esters by urea complexation and molecular distillation.","volume":"99","author":"Magallanes","year":"2019","journal-title":"J Sci Food Agric."},{"key":"B12","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1016\/j.renene.2018.10.081","article-title":"Synthesis and optimization of ethyl esters from fish oil waste for biodiesel production.","volume":"133","author":"Costa Cardoso","year":"2019","journal-title":"Renew. Energy."},{"key":"B13","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.jnutbio.2017.09.024","article-title":"Dietary fish oil differentially ameliorates high-fructose diet-induced hepatic steatosis and hyperlipidemia in mice depending on time of feeding.","volume":"52","author":"Oishi","year":"2018","journal-title":"J Nutr Biochem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"101729","DOI":"10.1016\/j.algal.2019.101729","article-title":"Obtaining highly pure EPA-rich lipids from dry and wet Nannochloropsis gaditana microalgal biomass using ethanol, hexane and acetone.","volume":"45","author":"Jim\u00e9nez Callej\u00f3n","year":"2020","journal-title":"Algal Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"102586","DOI":"10.1016\/j.algal.2021.102586","article-title":"Supercritical fluid extraction and pressurized liquid extraction processes applied to eicosapentaenoic acid-rich polar lipid recovery from the microalga Nannochloropsis sp.","volume":"61","author":"Jim\u00e9nez Callej\u00f3n","year":"2022","journal-title":"Algal Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1016\/j.renene.2019.10.133","article-title":"Solvent screening and process optimization for high shear-assisted lipid extraction from wet cake of Nannochloropsis sp.","volume":"149","author":"Kwak","year":"2020","journal-title":"Renew. Energy."},{"key":"B17","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.biortech.2019.03.148","article-title":"Lipid extraction from wet Nannochloropsis biomass via enzyme-assisted three phase partitioning.","volume":"284","author":"Qiu","year":"2019","journal-title":"Bioresour Technol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1016\/j.supflu.2017.11.015","article-title":"Polyunsaturated \u03c9-3 and \u03c9-6 fatty acids, total carotenoids and antioxidant activity of three marine microalgae extracts obtained by supercritical CO2 and subcritical n-butane.","volume":"133","author":"Feller","year":"2018","journal-title":"J Supercrit Fluids."},{"key":"B19","doi-asserted-by":"publisher","first-page":"135223","DOI":"10.1016\/j.ijbiomac.2024.135223","article-title":"Extraction, purification, structural characterization and anti-hyperlipidemia activity of fucoidan from Laminaria digitata.","volume":"279","author":"Li","year":"2024","journal-title":"Int J Biol Macromol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.jff.2012.08.011","article-title":"Effects of the marine microalgae Isochrysis galbana and Nannochloropsis oculata in diabetic rats.","volume":"5","author":"Nunez","year":"2013","journal-title":"J Funct Foods."},{"key":"B21","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.plefa.2012.02.003","article-title":"Dietary long-chain polyunsaturated fatty acids upregulate expression of FADS3 transcripts.","volume":"88","author":"Reardon","year":"2013","journal-title":"Prostaglandins Leukot Essent Fatty Acids."},{"key":"B22","doi-asserted-by":"publisher","first-page":"177107","DOI":"10.1016\/j.ejphar.2024.177107","article-title":"The role for \u03c9-3 polyunsaturated and short chain fatty acids in hypertension: An updated view on the interaction with gut microbiota.","volume":"985","author":"Brosolo","year":"2024","journal-title":"Eur J Pharmacol."},{"key":"B23","doi-asserted-by":"crossref","first-page":"105155","DOI":"10.1016\/j.jff.2022.105155","article-title":"Haracterization and anti-diabetic evaluation of sulfated polysaccharide from Spirulina platensis.","volume":"95","author":"Liu","year":"2022","journal-title":"J Funct Foods."},{"key":"B24","doi-asserted-by":"publisher","first-page":"3032","DOI":"10.1093\/jn\/126.12.3032","article-title":"Supplementation with an algae source of docosahexaenoic acid increases (n-3) fatty acid status and alters selected risk factors for heart disease in vegetarian subjects.","volume":"126","author":"Conquer","year":"1996","journal-title":"J Nutr."},{"key":"B25","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/j.fct.2008.11.014","article-title":"An n-3 PUFA-rich microalgal oil diet protects to a similar extent as a fish oil-rich diet against AOM-induced colonic aberrant crypt foci in F344 rats.","volume":"47","author":"van Beelen","year":"2009","journal-title":"Food Chem Toxicol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.nutres.2022.07.006","article-title":"Dietary omega-6\/omega-3 ratio is not associated with gut microbiota composition and disease severity in patients with nonalcoholic fatty liver disease.","volume":"107","author":"Heinzer","year":"2022","journal-title":"Nutr Res."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2025.103932","article-title":"Low-carbohydrate diet enriched with omega-3 and omega-9 fatty acids modulates inflammation and lipid metabolism in the liver and white adipose tissue of a mouse model of obesity.","author":"Santamarina","year":"2025","journal-title":"Nutr Metab Cardiovasc Dis."},{"key":"B28","doi-asserted-by":"publisher","first-page":"110348","DOI":"10.1016\/j.abb.2025.110348","article-title":"The impact of oxidative stress on abnormal lipid metabolism-mediated disease development.","volume":"766","author":"Li","year":"2025","journal-title":"Arch Biochem Biophys."},{"key":"B29","doi-asserted-by":"publisher","first-page":"139808","DOI":"10.1016\/j.ijbiomac.2025.139808","article-title":"Structural characterization of polysaccharides from Polygonatum Sibiricum and effect on alleviating hyperlipidemia in egg yolk emulsion-induced mice.","volume":"296","author":"Zhao","year":"2025","journal-title":"Int J Biol Macromol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"103864","DOI":"10.1016\/j.jff.2020.103864","article-title":"Evidence on oleic acid and EPA + DHA role in retinal antioxidant defense, leukocyte adhesion, and vascular permeability: Insight from hyperlipidemic rat model.","volume":"67","author":"Bettadahalli","year":"2020","journal-title":"J Funct Foods."},{"key":"B31","doi-asserted-by":"publisher","first-page":"217469","DOI":"10.1016\/j.canlet.2025.217469","article-title":"LCAT deficiency promotes hepatocellular carcinoma progression and lenvatinib resistance by promoting triglyceride catabolism and fatty acid oxidation.","volume":"612","author":"Xu","year":"2025","journal-title":"Cancer Lett."}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2025.1615332\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T04:10:18Z","timestamp":1750911018000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2025.1615332\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,26]]},"references-count":31,"alternative-id":["10.3389\/fnut.2025.1615332"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2025.1615332","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,26]]},"article-number":"1615332"}}