{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T23:34:55Z","timestamp":1783726495575,"version":"3.55.0"},"reference-count":27,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T00:00:00Z","timestamp":1632873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2019M660383"],"award-info":[{"award-number":["2019M660383"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key-Area Research and Development Program of Guangdong Province","award":["2018B020206001, 2019B020212001"],"award-info":[{"award-number":["2018B020206001, 2019B020212001"]}]},{"name":"Guangdong Province Zhujiang Talent Program","award":["2019ZT08H476"],"award-info":[{"award-number":["2019ZT08H476"]}]},{"name":"Shenzhen Science and Technology Program","award":["KQTD20180412181334790"],"award-info":[{"award-number":["KQTD20180412181334790"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis, is one of the most common liver diseases worldwide. So far, no definitive medical treatment has been established to treat NAFLD except for lifestyle medication. Nitzschia laevis extract (NLE), a microalgal extract rich in fucoxanthin, has been previously demonstrated to reduce bodyweight in high-fat-diet (HFD) C57BL\/6J mice, indicating potential for prevention of NAFLD. In the present study, we investigated the lipid-lowering effects of NLE in HFD-induced steatosis murine model and palmitate-treated HepG2 cells. The results showed that NLE significantly lowered inguinal fat and attenuated hepatic steatosis in C57BL\/6J mice. Especially, NLE significantly prevented lipid accumulation in HepG2 cells. This was probably due to its capability to enhance hepatic mitochondrial function as evidenced by the increased oxygen consumption rate (OCR) and mitochondrial membrane potential (MMP), and repress fatty acid synthesis through phosphorylation of acetyl-CoA carboxylase (ACC). Moreover, fucoxanthin was identified to be responsible for the lipid-lowering effect of NLE. Taken together, NLE or other microalgal fucoxanthin-rich products are promising natural products that may help prevent against NAFLD.<\/jats:p>","DOI":"10.3390\/ph14101004","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T00:03:42Z","timestamp":1632960222000},"page":"1004","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Lipid-Lowering Bioactivity of Microalga Nitzschia laevis Extract Containing Fucoxanthin in Murine Model and Carcinomic Hepatocytes"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3471-168X","authenticated-orcid":false,"given":"Bingbing","family":"Guo","sequence":"first","affiliation":[{"name":"Faculty of Environment and Life, Beijing University of Technology, 100 Pingleyuan, Chaoyang District, Beijing 100124, China"},{"name":"Shenzhen Key Laboratory of Marine Microbiome Engineering, Institute for Advanced Study, Shenzhen University, Nanshan District, Shenzhen 518060, China"},{"name":"Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen 518060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Faculty of Environment and Life, Beijing University of Technology, 100 Pingleyuan, Chaoyang District, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Marine Microbiome Engineering, Institute for Advanced Study, Shenzhen University, Nanshan District, Shenzhen 518060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjin","family":"He","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Fujian Normal University, No.1, Keji Road, Fuzhou 350117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9054-943X","authenticated-orcid":false,"given":"Feng","family":"Chen","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Marine Microbiome Engineering, Institute for Advanced Study, Shenzhen University, Nanshan District, Shenzhen 518060, China"},{"name":"Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen 518060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka-Wing","family":"Cheng","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Marine Microbiome Engineering, Institute for Advanced Study, Shenzhen University, Nanshan District, Shenzhen 518060, China"},{"name":"Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen 518060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,29]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Distinct signatures of gut microbiome and metabolites associated with significant fibrosis in non-obese NAFLD","volume":"11","author":"Lee","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1001\/jama.2015.5370","article-title":"Nonalcoholic fatty liver disease: A systematic review","volume":"313","author":"Rinella","year":"2015","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"103857","DOI":"10.1016\/j.jff.2020.103857","article-title":"Lycopene prevents lipid accumulation in hepatocytes by stimulating PPAR\u03b1 and improving mitochondrial function","volume":"67","author":"Wang","year":"2020","journal-title":"J. Funct. Foods"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e1900811","DOI":"10.1002\/mnfr.201900811","article-title":"Green tea extract treatment in obese mice with nonalcoholic steatohepatitis restores the hepatic metabolome in association with limiting endotoxemia-TLR4-NF\u03baB-mediated inflammation","volume":"63","author":"Sasaki","year":"2019","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ni, Y., Zhuge, F., Nagashimada, M., and Ota, T. (2016). Novel action of carotenoids on non-alcoholic fatty liver disease: Macrophage polarization and liver homeostasis. Nutrients, 8.","DOI":"10.3390\/nu8070391"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3760","DOI":"10.1111\/bph.15099","article-title":"Astaxanthin attenuates hepatic damage and mitochondrial dysfunction in non-alcoholic fatty liver disease by up-regulating the FGF21\/PGC-1\u03b1 pathway","volume":"177","author":"Wu","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1800808","DOI":"10.1002\/mnfr.201800808","article-title":"Extract of the microalga Nitzschia laevis prevents high-fat-diet-induced obesity in mice by modulating the composition of gut microbiota","volume":"63","author":"Guo","year":"2019","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.bbrc.2020.05.050","article-title":"Fucoxanthin inhibits hepatic oxidative stress, inflammation, and fibrosis in diet-induced nonalcoholic steatohepatitis model mice","volume":"528","author":"Takatani","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1194\/jlr.M085613","article-title":"Mitochondrial dysfunction-related lipid changes occur in nonalcoholic fatty liver disease progression","volume":"59","author":"Peng","year":"2018","journal-title":"J. Lipid Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"102336","DOI":"10.1016\/j.ceca.2020.102336","article-title":"Role of mitochondria in liver metabolic health and diseases","volume":"94","author":"Morio","year":"2021","journal-title":"Cell Calcium"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1080\/13543784.2020.1668374","article-title":"Gs-0976 (firsocostat): An investigational liver-directed acetyl-coa carboxylase (ACC) inhibitor for the treatment of non-alcoholic steatohepatitis (NASH)","volume":"29","author":"Alkhouri","year":"2020","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.cmet.2018.08.020","article-title":"Inhibition of acetyl-coa carboxylase by phosphorylation or the inhibitor ND-654 suppresses lipogenesis and hepatocellular carcinoma","volume":"29","author":"Lally","year":"2019","journal-title":"Cell Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/s41575-020-00381-6","article-title":"Global epidemiology of NAFLD-related hcc: Trends, predictions, risk factors and prevention","volume":"18","author":"Huang","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1053\/j.gastro.2015.04.005","article-title":"Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis","volume":"149","author":"Friedman","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/j.1463-1326.2009.01132.x","article-title":"The effects of xanthigen in the weight management of obese premenopausal women with non-alcoholic fatty liver disease and normal liver fat","volume":"12","author":"Abidov","year":"2010","journal-title":"Diabetes Obes. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5644","DOI":"10.1039\/C9FO01018A","article-title":"Fucoxanthin modulates cecal and fecal microbiota differently based on diet","volume":"10","author":"Guo","year":"2019","journal-title":"Food Funct."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.bbrc.2017.11.022","article-title":"Fucoxanthin attenuates fatty acid-induced lipid accumulation in FL83B hepatocytes through regulated Sirt1\/AMPK signaling pathway","volume":"495","author":"Chang","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.cmet.2015.04.004","article-title":"Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis","volume":"21","author":"Koliaki","year":"2015","journal-title":"Cell Metab."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Sinton, M.C., Meseguer-Ripolles, J., Lucendo-Villarin, B., Lyall, M.J., Carter, R.N., Morton, N.M., Hay, D.C., and Drake, A.J. (2020). Nonalcoholic fatty liver disease is associated with decreased hepatocyte mitochondrial respiration but not mitochondrial number. bioRxiv.","DOI":"10.1101\/2020.03.10.985200"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1089\/ars.2017.7172","article-title":"Dihydromyricetin ameliorates nonalcoholic fatty liver disease by improving mitochondrial respiratory capacity and redox homeostasis through modulation of SIRT3 signaling","volume":"30","author":"Zeng","year":"2019","journal-title":"Antioxid. Redox Signal."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Albracht-Schulte, K., Gonzalez, S., Jackson, A., Wilson, S., Ramalingam, L., Kalupahana, N.S., and Moustaid-Moussa, N. (2019). Eicosapentaenoic acid improves hepatic metabolism and reduces inflammation independent of obesity in high-fat-fed mice and in HepG2 cells. Nutrients, 11.","DOI":"10.3390\/nu11030599"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ab.2017.07.009","article-title":"Mitochondrial membrane potential","volume":"552","author":"Zorova","year":"2017","journal-title":"Anal. Biochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1800795","DOI":"10.1002\/mnfr.201800795","article-title":"Sulforaphane improves lipid metabolism by enhancing mitochondrial function and biogenesis in vivo and in vitro","volume":"63","author":"Lei","year":"2019","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4128","DOI":"10.1016\/S0021-9258(17)34693-8","article-title":"Carnitine palmitoyltransferase i. The site of inhibition of hepatic fatty acid oxidation by malonyl-CoA","volume":"253","author":"McGarry","year":"1978","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Guo, B., Liu, B., Yang, B., Sun, P., Lu, X., Liu, J., and Chen, F. (2016). Screening of diatom strains and characterization of cyclotella cryptica as a potential fucoxanthin producer. Mar. Drugs, 14.","DOI":"10.3390\/md14070125"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.abb.2014.12.009","article-title":"Palmitate induces insulin resistance in human hepg2 hepatocytes by enhancing ubiquitination and proteasomal degradation of key insulin signaling molecules","volume":"566","author":"Ishii","year":"2015","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"111171","DOI":"10.1016\/j.fct.2020.111171","article-title":"Obesogenic effects of chlorpyrifos and its metabolites during the differentiation of 3T3-L1 preadipocytes","volume":"137","author":"Blanco","year":"2020","journal-title":"Food Chem. Toxicol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/10\/1004\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:07:36Z","timestamp":1760166456000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/10\/1004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,29]]},"references-count":27,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["ph14101004"],"URL":"https:\/\/doi.org\/10.3390\/ph14101004","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,29]]}}}