{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T15:10:22Z","timestamp":1782141022745,"version":"3.54.5"},"reference-count":30,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2017,5,28]],"date-time":"2017-05-28T00:00:00Z","timestamp":1495929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Annual wormwood (AW) (Artemisia annua L.) has anti-malarial, anti-bacterial, anti-oxidant, anti-tumour, and anti-inflammatory activities. In the present study, we evaluated the effects of annual wormwood leaves (AWL) on adipocyte differentiation in 3T3-L1 cells and high-fat diet (HFD)-induced obese rats. 3T3-L1 adipocytes and HFD-induced obese rats were treated with AWL, and its effect on gene expression was analyzed using RT-PCR and Western blotting experiments. Treatment with AWL effectively prevented triglyceride accumulation during adipogenesis in a dose-dependent manner. Consistently, AWL suppressed the differentiation of 3T3-L1 preadipocytes into adipocytes through the downregulation of dexamethasone, 3-isobutyl-1- methylxanthine, and insulin (DMI)-induced serine\/threonine kinase protein kinase B (PKB\/Akt) activation and the expression of adipogenic genes, including the CCAAT\/enhancer binding protein-\u03b1 (C\/EBP\u03b1) and peroximal proliferator-activated receptor-\u03b3 (PPAR\u03b3). Moreover, the expression of adipocyte fatty acid-binding protein 4 (aP2), which is a known PPAR\u03b3-target gene, was downregulated by AWL treatment. Oral administration of AWL extracts significantly decreased the body weight gain, adipose tissue mass, adipocyte cell size, serum triglyceride (TG), and total cholesterol (TC) levels in HFD-induced obese rats. These results provide novel insight into the molecular mechanisms underlying the anti-obesity effects of AWL that are mediated by the downregulation of the expression of major adipogenic transcription factors, C\/EBP\u03b1 and PPAR\u03b3 and Akt signalling.<\/jats:p>","DOI":"10.3390\/nu9060554","type":"journal-article","created":{"date-parts":[[2017,5,30]],"date-time":"2017-05-30T04:35:42Z","timestamp":1496118942000},"page":"554","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Annual Wormwood Leaf Inhibits the Adipogenesis of 3T3-L1 and Obesity in High-Fat Diet-Induced Obese Rats"],"prefix":"10.3390","volume":"9","author":[{"given":"Yuno","family":"Song","sequence":"first","affiliation":[{"name":"Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo-Jung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Foods and Nutrition, Gyeongsang National University, Jinju 660-701, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun-Hee","family":"Jang","sequence":"additional","affiliation":[{"name":"Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Food Science and Biotechnology, Daegu University, Gyungsan 712-714, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Duck","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Science, New York Medical College, Valhalla, NY 10595, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Woo","family":"Kim","sequence":"additional","affiliation":[{"name":"Animal Genetic Resources Station, National Institute of Animal Science, RDA, Namwon 590-832, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3105-1869","authenticated-orcid":false,"given":"Chung-Kil","family":"Won","sequence":"additional","affiliation":[{"name":"Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Hyeon","family":"Cho","sequence":"additional","affiliation":[{"name":"Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1038\/sj.ijo.0803502","article-title":"Evidence of anti-obesity effects of the pomegranate leaf extract in high-fat diet induced obese mice","volume":"31","author":"Lei","year":"2007","journal-title":"Int. J. Obes. Lond."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.cell.2005.11.026","article-title":"The Many Faces of PPAR\u03b3","volume":"16","author":"Lehrke","year":"2005","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Moseti, D., Regassa, A., and Kim, W.K. (2016). Molecular Regulation of Adipogenesis and Potential Anti-Adipogenic Bioactive Molecules. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17010124"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1074\/jbc.270.2.647","article-title":"Insulin Regulates Transcription of the CCAAT\/Enhancer Binding Protein (C\/EBP) \u03b1, \u03b2, and \u03b4 genes in Fully-differentiated 3T3-L1 Adipocytes","volume":"13","author":"MacDougald","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.biochi.2009.02.002","article-title":"The role of C\/EBPdelta in the early stages of adipogenesis","volume":"91","author":"Hishida","year":"2009","journal-title":"Biochimie"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1101\/gad.14.11.1293","article-title":"Transcriptional regulation of adipogenesis","volume":"14","author":"Rosen","year":"2000","journal-title":"Genes Dev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.cmet.2006.07.001","article-title":"Transcriptional control of adipocyte formation","volume":"4","author":"Farmer","year":"2006","journal-title":"Cell Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"28080","DOI":"10.1038\/srep28080","article-title":"Thioredoxin reductase 1 suppresses adipocyte differentiation and insulin responsiveness","volume":"6","author":"Peng","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1242\/jcs.02792","article-title":"PKB\u03b1 is required for adipose differentiation of mouse embryonic fibroblasts","volume":"119","author":"Baudry","year":"2006","journal-title":"J. Cell Sci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Zhang, H.H., Huang, J., D\u00fcvel, K., Boback, B., Wu, S., Squillace, R.M., Wu, C.L., and Manning, B.D. (2009). Insulin Stimulates Adipogenesis through the Akt-TSC2-mTORC1 Pathway. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006189"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/378785a0","article-title":"Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B","volume":"378","author":"Cross","year":"1995","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"21","DOI":"10.4196\/kjpp.2015.19.1.21","article-title":"Anti-inflammatory, Antioxidant and Antimicrobial Effects of Artemisinin Extracts from Artemisia annua L.","volume":"19","author":"Kim","year":"2015","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1055\/s-2007-967138","article-title":"Willmar Schwabe Award 2006: Antiplasmodial and antitumor activity of artemisinin\u2014From bench to bedside","volume":"73","author":"Efferth","year":"2007","journal-title":"Planta Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.niox.2008.04.008","article-title":"Effect of artemisinins and other endoperoxides on nitric oxide-related signaling pathway in RAW 264.7 mouse macrophage cells","volume":"19","author":"Konkimalla","year":"2008","journal-title":"Nitric Oxide"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.3390\/molecules15053135","article-title":"Flavonoids from Artemisia annua L. as antioxidants and their potential synergism with artemisinin against malaria and cancer","volume":"15","author":"Ferreira","year":"2010","journal-title":"Molecules"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1002\/jcb.24124","article-title":"Artemisinic acid is a regulator of adipocyte differentiation and C\/EBP \u03b4 expression","volume":"113","author":"Lee","year":"2012","journal-title":"J. Cell. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.foodchem.2012.02.101","article-title":"Anti-obesity effect of Schisandra chinensis in 3T3-L1 cells and high fat diet-induced obese rats","volume":"134","author":"Park","year":"2012","journal-title":"Food Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1093\/jn\/136.2.433","article-title":"A mixture of the Salacia reticulata (Kotala himbutu) aqueous extract and cyclodextrin reduces the accumulation of visceral fat mass in mice and rats with high-fat diet-induced obesity","volume":"136","author":"Kishino","year":"2006","journal-title":"J. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1517\/14656560802678138","article-title":"Antiviral treatment of cytomegalovirus infection and resistant strains","volume":"10","author":"Schreiber","year":"2009","journal-title":"Exp. Opin. Pharmacother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.pharmthera.2013.12.001","article-title":"Artemisinins: Pharmacological actions beyond anti-malarial","volume":"142","author":"Ho","year":"2014","journal-title":"Pharmacol. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3778","DOI":"10.1002\/jcp.24086","article-title":"Artesunate induces apoptosis via a Bak-mediated caspase-independent intrinsic pathway in human lung adenocarcinoma cells","volume":"227","author":"Zhou","year":"2012","journal-title":"J. Cell. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2886","DOI":"10.3390\/molecules15042886","article-title":"Pharmacogenomic identification of c-Myc\/Max-regulated genes associated with cytotoxicity of artesunate towards human colon, ovarian and lung cancer cell lines","volume":"15","author":"Sertel","year":"2010","journal-title":"Molecules"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.ejcb.2013.06.001","article-title":"Adipocyte and adipogenesis","volume":"92","author":"Ali","year":"2013","journal-title":"Eur. J. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/nrm2066","article-title":"Adipocyte differentiation from the inside out","volume":"7","author":"Rosen","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1172\/JCI200419900","article-title":"PPAR\u03b3 insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors","volume":"113","author":"Akune","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1152\/physrev.1998.78.3.783","article-title":"Understanding adipocyte differentiation","volume":"78","author":"Gregoire","year":"1998","journal-title":"Physiol. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"35914","DOI":"10.1074\/jbc.M402297200","article-title":"Protein kinase B\/AKT 1 plays a pivotal role in insulin-like growth factor-1 receptor signaling induced 3T3-L1 adipocyte differentiation","volume":"279","author":"Xu","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"31372","DOI":"10.1074\/jbc.271.49.31372","article-title":"Expression of a constitutively active Akt Ser\/Thr kinase in 3T3-L1 adipocytes stimulates glucose uptake and glucose transporter 4 translocation","volume":"271","author":"Kohn","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3590","DOI":"10.1210\/endo.137.8.8754791","article-title":"Expression of a constitutively activated form of protein kinase B (c-Akt) in 3T3-L1 preadipose cells causes spontaneous differentiation","volume":"137","author":"Magun","year":"1996","journal-title":"Endocrinology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1101\/gad.1089403","article-title":"Dwarfism, impaired skin development, skeletal muscle atrophy, delayed bone development, and impeded adipogenesis in mice lacking Akt1 and Akt2","volume":"17","author":"Peng","year":"2003","journal-title":"Genes Dev."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/9\/6\/554\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:37:15Z","timestamp":1760207835000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/9\/6\/554"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,28]]},"references-count":30,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2017,6]]}},"alternative-id":["nu9060554"],"URL":"https:\/\/doi.org\/10.3390\/nu9060554","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,28]]}}}