{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:04:14Z","timestamp":1789517054401,"version":"build-2803163510"},"reference-count":69,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T00:00:00Z","timestamp":1601337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2014M3A9C4066462"],"award-info":[{"award-number":["NRF-2014M3A9C4066462"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2014M3A9C4066459"],"award-info":[{"award-number":["NRF-2014M3A9C4066459"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The Chrysanthemum morifolium Ramat (CM) is widely used as a traditional medicine and herbal tea by the Asian population for its health benefits related to obesity. However, compared to the flowers of CM, detailed mechanisms underlying the beneficial effects of its leaves on obesity and dyslipidemia have not yet been elucidated. Therefore, to investigate the lipidomic biomarkers responsible for the pharmacological effects of CM leaf extract (CLE) in plasma of mice fed a high-fat diet (HFD), the plasma of mice fed a normal diet (ND), HFD, HFD plus CLE 1.5% diet, and HFD plus luteolin 0.003% diet (LU) for 16 weeks were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS\/MS) combined with multivariate analysis. In our analysis, the ND, HFD, CLE, and LU groups were clearly differentiated by partial least-squares discriminant analysis (PLS-DA) score plots. The major metabolites contributing to this differentiation were cholesteryl esters (CEs), lysophosphatidylcholines (LPCs), phosphatidylcholines (PCs), ceramides (CERs), and sphingomyelins (SMs). The levels of plasma CEs, LPCs, PCs, SMs, and CERs were significantly increased in the HFD group compared to those in the ND group, and levels of these lipids recovered to normal after administration of CLE or LU. Furthermore, changes in hepatic mRNA expression levels involved in the Kennedy pathway and sphingolipid biosynthesis were also suppressed by treatment with CLE or LU. In conclusion, this study examined the beneficial effects of CLE and LU on obesity and dyslipidemia, which were demonstrated as reduced synthesis of lipotoxic intermediates. These results may provide valuable insights towards evaluating the therapeutic effects of CLE and LU and understanding obesity-related diseases.<\/jats:p>","DOI":"10.3390\/nu12102973","type":"journal-article","created":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T08:43:27Z","timestamp":1601369007000},"page":"2973","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Plasma Lipidomics Reveals Insights into Anti-Obesity Effect of Chrysanthemum morifolium Ramat Leaves and Its Constituent Luteolin in High-Fat Diet-Induced Dyslipidemic Mice"],"prefix":"10.3390","volume":"12","author":[{"given":"Jong Cheol","family":"Shon","sequence":"first","affiliation":[{"name":"Environmental Chemistry Research Group, Korea Institute of Toxicology, Jinju 52834, Korea"},{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Cheol","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3414-8399","authenticated-orcid":false,"given":"Ri","family":"Ryu","sequence":"additional","affiliation":[{"name":"Research Institute of Eco-Friendly Livestock Science, Institute of Green-Bio Science and Technology, Seoul National University, Pyeongchang 25354, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhexue","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Su","family":"Seo","sequence":"additional","affiliation":[{"name":"Environmental Chemistry Research Group, Korea Institute of Toxicology, Jinju 52834, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myung-Sook","family":"Choi","sequence":"additional","affiliation":[{"name":"Center for Food and Nutritional Genomics Research, Kyungpook National University, Daegu 41566, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3285-5594","authenticated-orcid":false,"given":"Kwang-Hyeon","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Cheng, H., Xu, N., Zhao, W., Su, J., Liang, M., Xie, Z., Wu, X., and Li, Q. (2017). (-)-Epicatechin regulates blood lipids and attenuates hepatic steatosis in rats fed high-fat diet. Mol. Nutr. Food Res., 61.","DOI":"10.1002\/mnfr.201700303"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1056\/NEJMoa1614362","article-title":"Health Effects of Overweight and Obesity in 195 Countries over 25 Years","volume":"377","author":"Collaborators","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jacc.2017.11.011","article-title":"Obesity: Pathophysiology and Management","volume":"71","author":"Gadde","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s12986-016-0123-9","article-title":"Animal models of metabolic syndrome: A review","volume":"13","author":"Wong","year":"2016","journal-title":"Nutr. Metab. Lond."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/978-1-61779-430-8_27","article-title":"A mouse model of diet-induced obesity and insulin resistance","volume":"821","author":"Wang","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1038\/oby.2007.608","article-title":"High-fat diets: Modeling the metabolic disorders of human obesity in rodents","volume":"15","author":"Buettner","year":"2007","journal-title":"Obesity"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1254721","DOI":"10.1155\/2017\/1254721","article-title":"Quantification of Antioxidant Phenolic Compounds in a New Chrysanthemum Cultivar by High-Performance Liquid Chromatography with Diode Array Detection and Electrospray Ionization Mass Spectrometry","volume":"2017","author":"Han","year":"2017","journal-title":"Int. J. Anal. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1055\/s-2005-873115","article-title":"Identification of new dicaffeoylquinic acids from Chrysanthemum morifolium and their antioxidant activities","volume":"71","author":"Kim","year":"2005","journal-title":"Planta Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.foodchem.2019.02.013","article-title":"Chemical compositions of chrysanthemum teas and their anti-inflammatory and antioxidant properties","volume":"286","author":"Li","year":"2019","journal-title":"Food Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S0304-3835(01)00769-8","article-title":"Constituents of Compositae plants III. Anti-tumor promoting effects and cytotoxic activity against human cancer cell lines of triterpene diols and triols from edible chrysanthemum flowers","volume":"177","author":"Ukiya","year":"2002","journal-title":"Cancer Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.1080\/13880209.2016.1190764","article-title":"Chrysanthemum morifolium extract improves hypertension-induced cardiac hypertrophy in rats by reduction of blood pressure and inhibition of myocardial hypoxia inducible factor-1alpha expression","volume":"54","author":"Gao","year":"2016","journal-title":"Pharm. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.nutres.2013.12.010","article-title":"Chrysanthemum morifolium extract attenuates high-fat milk-induced fatty liver through peroxisome proliferator-activated receptor alpha-mediated mechanism in mice","volume":"34","author":"Cui","year":"2014","journal-title":"Nutr. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1142\/S0192415X18500076","article-title":"Chrysanthemum indicum Inhibits Adipogenesis and Activates the AMPK Pathway in High-Fat-Diet-Induced Obese Mice","volume":"46","author":"Nepali","year":"2018","journal-title":"Am. J. Chin. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jab.2016.10.001","article-title":"Hypoglycemic effect of Chrysanthemum morifolium extract on alloxan-induced diabetic mice is associated with peroxisome proliferator-activated receptor \u03b1\/\u03b3-mediated hepatic glycogen synthesis","volume":"15","author":"Shang","year":"2017","journal-title":"J. Appl. Biomed."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.jchromb.2006.10.028","article-title":"Identification and characterization of major flavonoids and caffeoylquinic acids in three Compositae plants by LC\/DAD-APCI\/MS","volume":"848","author":"Lai","year":"2007","journal-title":"J. Chromatogr. B Anal. Technol. Biomed Life Sci."},{"key":"ref_16","first-page":"1670","article-title":"Comparison of major bioactive components from leaves of Chrysanthemum morifolium","volume":"40","author":"Wang","year":"2015","journal-title":"China J. Chin. Mater. Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ryu, R., Kwon, E.Y., Choi, J.Y., Shon, J.C., Liu, K.H., and Choi, M.S. (2019). Chrysanthemum Leaf Ethanol Extract Prevents Obesity and Metabolic Disease in Diet-Induced Obese Mice via Lipid Mobilization in White Adipose Tissue. Nutrients, 11.","DOI":"10.3390\/nu11061347"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.chembiol.2018.10.008","article-title":"High-Throughput Plasma Lipidomics: Detailed Mapping of the Associations with Cardiometabolic Risk Factors","volume":"26","author":"Huynh","year":"2019","journal-title":"Cell Chem. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s11306-010-0207-x","article-title":"Lipidomic analysis of variation in response to simvastatin in the Cholesterol and Pharmacogenetics Study","volume":"6","author":"Baillie","year":"2010","journal-title":"Metabolomics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"22151","DOI":"10.1038\/srep22151","article-title":"An integrated lipidomics and metabolomics reveal nephroprotective effect and biochemical mechanism of Rheum officinale in chronic renal failure","volume":"6","author":"Zhang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.jdiacomp.2018.05.014","article-title":"Exploratory lipidomics in patients with nascent Metabolic Syndrome","volume":"32","author":"Ramakrishanan","year":"2018","journal-title":"J. Diabetes Complicat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"13538","DOI":"10.1074\/jbc.M709950200","article-title":"Protection from high fat diet-induced increase in ceramide in mice lacking plasminogen activator inhibitor 1","volume":"283","author":"Shah","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.3390\/ijms15022991","article-title":"Lipidomic analysis of serum from high fat diet induced obese mice","volume":"15","author":"Eisinger","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"973","DOI":"10.3389\/fphar.2018.00973","article-title":"Cyclocarya paliurus Leaves Tea Improves Dyslipidemia in Diabetic Mice: A Lipidomics-Based Network Pharmacology Study","volume":"9","author":"Zhai","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jnutbio.2017.09.002","article-title":"Effect of green tea on hepatic lipid metabolism in mice fed a high-fat diet","volume":"51","author":"Nam","year":"2018","journal-title":"J. Nutr. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2919","DOI":"10.1021\/jf506216p","article-title":"Direct infusion MS-based lipid profiling reveals the pharmacological effects of compound K-reinforced ginsenosides in high-fat diet induced obese mice","volume":"63","author":"Shon","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_27","first-page":"183","article-title":"Effect of different extracting methods on quality of Chrysanthemum Morifolium Ramat. Infusion","volume":"16 (Suppl. 1)","author":"Ye","year":"2007","journal-title":"Asia Pac. J. Clin. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.jep.2011.01.002","article-title":"LC-MS\/MS determination and pharmacokinetic study of five flavone components after solvent extraction\/acid hydrolysis in rat plasma after oral administration of Verbena officinalis L. extract","volume":"135","author":"Duan","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.foodchem.2009.09.083","article-title":"Identification of the phenolic components of chrysanthemum flower (Chrysanthemum morifolium Ramat)","volume":"120","author":"Lin","year":"2010","journal-title":"Food Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"593","DOI":"10.3390\/12030593","article-title":"Characterization of flavonoid subgroups and hydroxy substitution by HPLC-MS\/MS","volume":"12","author":"Tsimogiannis","year":"2007","journal-title":"Molecules"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1194\/jlr.D700041-JLR200","article-title":"Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics","volume":"49","author":"Matyash","year":"2008","journal-title":"J. Lipid Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"110254","DOI":"10.1016\/j.ecoenv.2020.110254","article-title":"The impact of phenanthrene on membrane phospholipids and its biodegradation by Sphingopyxis soli","volume":"192","author":"Shon","year":"2020","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Im, S.S., Park, H.Y., Shon, J.C., Chung, I.S., Cho, H.C., Liu, K.H., and Song, D.K. (2019). Plasma sphingomyelins increase in pre-diabetic Korean men with abdominal obesity. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0213285"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.trac.2014.04.017","article-title":"Comprehensive analysis of lipids in biological systems by liquid chromatography-mass spectrometry","volume":"61","author":"Cajka","year":"2014","journal-title":"Trends Anal. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"12360","DOI":"10.1021\/acs.analchem.7b03404","article-title":"Validating Quantitative Untargeted Lipidomics Across Nine Liquid Chromatography-High-Resolution Mass Spectrometry Platforms","volume":"89","author":"Cajka","year":"2017","journal-title":"Anal. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1172\/JCI124159","article-title":"DEGS1-associated aberrant sphingolipid metabolism impairs nervous system function in humans","volume":"129","author":"Karsai","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1038\/nprot.2012.016","article-title":"Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks","volume":"7","author":"Trapnell","year":"2012","journal-title":"Nat. Protoc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1038\/nprot.2010.50","article-title":"Global metabolic profiling procedures for urine using UPLC-MS","volume":"5","author":"Want","year":"2010","journal-title":"Nat. Protoc."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1194\/jlr.S087163","article-title":"MS-based lipidomics of human blood plasma: A community-initiated position paper to develop accepted guidelines","volume":"59","author":"Burla","year":"2018","journal-title":"J. Lipid Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1007\/s00216-020-02576-x","article-title":"Evaluation of lipid quantification accuracy using HILIC and RPLC MS on the example of NIST(R) SRM(R) 1950 metabolites in human plasma","volume":"412","author":"Lange","year":"2020","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1002\/cem.1187","article-title":"CV-ANOVA for significance testing of PLS and OPLS\u00ae models","volume":"22","author":"Eriksson","year":"2008","journal-title":"J. Chemom."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.jnutbio.2018.10.005","article-title":"Dietary saturated fatty acid type impacts obesity-induced metabolic dysfunction and plasma lipidomic signatures in mice","volume":"64","author":"Zacek","year":"2019","journal-title":"J. Nutr. Biochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1002\/mnfr.201200700","article-title":"Effect of fermented soybean product (Cheonggukjang) intake on metabolic parameters in mice fed a high-fat diet","volume":"57","author":"Kim","year":"2013","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1021\/pr100892r","article-title":"Metabolomic analysis of livers and serum from high-fat diet induced obese mice","volume":"10","author":"Kim","year":"2011","journal-title":"J. Proteome Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1016\/j.bbamem.2017.04.006","article-title":"The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease","volume":"1859","author":"Kennelly","year":"2017","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Petkevicius, K., Virtue, S., Bidault, G., Jenkins, B., Cubuk, C., Morgantini, C., Aouadi, M., Dopazo, J., Serlie, M.J., and Koulman, A. (2019). Accelerated phosphatidylcholine turnover in macrophages promotes adipose tissue inflammation in obesity. Elife, 8.","DOI":"10.7554\/eLife.47990"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"22403","DOI":"10.1074\/jbc.M110.108514","article-title":"Impaired de novo choline synthesis explains why phosphatidylethanolamine N-methyltransferase-deficient mice are protected from diet-induced obesity","volume":"285","author":"Jacobs","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1161\/ATVBAHA.109.188672","article-title":"Lack of phosphatidylethanolamine N-methyltransferase alters plasma VLDL phospholipids and attenuates atherosclerosis in mice","volume":"29","author":"Zhao","year":"2009","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"358","DOI":"10.2337\/db15-0659","article-title":"Skeletal Muscle Phospholipid Metabolism Regulates Insulin Sensitivity and Contractile Function","volume":"65","author":"Funai","year":"2016","journal-title":"Diabetes"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1002\/hep.23719","article-title":"Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: The central role of nontriglyceride fatty acid metabolites","volume":"52","year":"2010","journal-title":"Hepatology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.atherosclerosis.2009.05.029","article-title":"Metabolism and atherogenic disease association of lysophosphatidylcholine","volume":"208","author":"Schmitz","year":"2010","journal-title":"Atherosclerosis"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Law, S.H., Chan, M.L., Marathe, G.K., Parveen, F., Chen, C.H., and Ke, L.Y. (2019). An Updated Review of Lysophosphatidylcholine Metabolism in Human Diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051149"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1161\/CIRCULATIONAHA.113.002500","article-title":"Lipidomics profiling and risk of cardiovascular disease in the prospective population-based Bruneck study","volume":"129","author":"Stegemann","year":"2014","journal-title":"Circulation"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1161\/CIRCULATIONAHA.116.023233","article-title":"Plasma Lipidomic Profiles Improve on Traditional Risk Factors for the Prediction of Cardiovascular Events in Type 2 Diabetes Mellitus","volume":"134","author":"Alshehry","year":"2016","journal-title":"Circulation"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3074","DOI":"10.1194\/jlr.D008532","article-title":"Blood sphingolipidomics in healthy humans: Impact of sample collection methodology","volume":"51","author":"Hammad","year":"2010","journal-title":"J. Lipid Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2579","DOI":"10.2337\/db06-0330","article-title":"Altered adipose and plasma sphingolipid metabolism in obesity: A potential mechanism for cardiovascular and metabolic risk","volume":"55","author":"Samad","year":"2006","journal-title":"Diabetes"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"E211","DOI":"10.1152\/ajpendo.91014.2008","article-title":"Central role of ceramide biosynthesis in body weight regulation, energy metabolism, and the metabolic syndrome","volume":"297","author":"Yang","year":"2009","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Kasumov, T., Li, L., Li, M., Gulshan, K., Kirwan, J.P., Liu, X., Previs, S., Willard, B., Smith, J.D., and McCullough, A. (2015). Ceramide as a mediator of non-alcoholic Fatty liver disease and associated atherosclerosis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0126910"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"25","DOI":"10.2337\/diabetes.53.1.25","article-title":"Ceramide content is increased in skeletal muscle from obese insulin-resistant humans","volume":"53","author":"Adams","year":"2004","journal-title":"Diabetes"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Cowart, L.A. (2011). Sphingolipids and Metabolic Disease, Springer Science & Business Media.","DOI":"10.1007\/978-1-4614-0650-1"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1111\/j.1872-034X.2011.00934.x","article-title":"High fat diet induced hepatic steatosis and insulin resistance: Role of dysregulated ceramide metabolism","volume":"42","author":"Longato","year":"2012","journal-title":"Hepatol. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/hep.26606","article-title":"Hepatic cannabinoid-1 receptors mediate diet-induced insulin resistance by increasing de novo synthesis of long-chain ceramides","volume":"59","author":"Cinar","year":"2014","journal-title":"Hepatology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.cmet.2014.08.002","article-title":"Obesity-induced CerS6-dependent C16:0 ceramide production promotes weight gain and glucose intolerance","volume":"20","author":"Turpin","year":"2014","journal-title":"Cell Metab."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.molmet.2018.12.008","article-title":"The role of C16:0 ceramide in the development of obesity and type 2 diabetes: CerS6 inhibition as a novel therapeutic approach","volume":"21","author":"Raichur","year":"2019","journal-title":"Mol. Metab."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.cmet.2014.09.015","article-title":"CerS2 haploinsufficiency inhibits beta-oxidation and confers susceptibility to diet-induced steatohepatitis and insulin resistance","volume":"20","author":"Raichur","year":"2014","journal-title":"Cell Metab."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1096\/fj.201601156R","article-title":"Ceramides and mitochondrial fatty acid oxidation in obesity","volume":"31","author":"Fucho","year":"2017","journal-title":"FASEB J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1161\/ATVBAHA.112.251538","article-title":"Impact of sphingomyelin synthase 1 deficiency on sphingolipid metabolism and atherosclerosis in mice","volume":"32","author":"Li","year":"2012","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"28544","DOI":"10.1074\/jbc.M111.255646","article-title":"Dynamic modification of sphingomyelin in lipid microdomains controls development of obesity, fatty liver, and type 2 diabetes","volume":"286","author":"Mitsutake","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1161\/ATVBAHA.113.301498","article-title":"Sphingomyelin synthase 2 activity and liver steatosis: An effect of ceramide-mediated peroxisome proliferator-activated receptor gamma2 suppression","volume":"33","author":"Li","year":"2013","journal-title":"Arter. Thromb. Vasc. 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