{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:54:46Z","timestamp":1787507686440,"version":"build-2736575974"},"reference-count":56,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T00:00:00Z","timestamp":1676246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["321428"],"award-info":[{"award-number":["321428"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["0245896-3"],"award-info":[{"award-number":["0245896-3"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sigrid Juselius Foundation","award":["321428"],"award-info":[{"award-number":["321428"]}]},{"name":"Sigrid Juselius Foundation","award":["0245896-3"],"award-info":[{"award-number":["0245896-3"]}]},{"name":"Finnish Foundation for Cardiovascular Research","award":["321428"],"award-info":[{"award-number":["321428"]}]},{"name":"Finnish Foundation for Cardiovascular Research","award":["0245896-3"],"award-info":[{"award-number":["0245896-3"]}]},{"name":"Centre of Excellence of Cardiovascular and Metabolic Diseases","award":["321428"],"award-info":[{"award-number":["321428"]}]},{"name":"Centre of Excellence of Cardiovascular and Metabolic Diseases","award":["0245896-3"],"award-info":[{"award-number":["0245896-3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Both genetic and non-genetic factors are important in the pathophysiology of non-alcoholic fatty liver disease (NAFLD). The aim of our study was to identify novel metabolites and pathways associated with NAFLD by including both genetic and non-genetic factors in statistical analyses. We genotyped six genetic variants in the PNPLA3, TM6SF2, MBOAT7, GCKR, PPP1R3B, and HSD17B13 genes reported to be associated with NAFLD. Non-targeted metabolomic profiling was performed from plasma samples. We applied a previously validated fatty liver index to identify participants with NAFLD. First, we associated the six genetic variants with 1098 metabolites in 2 339 men without NAFLD to determine the effects of the genetic variants on metabolites, and then in 2 535 men with NAFLD to determine the joint effects of genetic variants and non-genetic factors on metabolites. We identified several novel metabolites and metabolic pathways, especially for PNPLA3, GCKR, and PPP1R38 variants relevant to the pathophysiology of NAFLD. Importantly, we showed that each genetic variant for NAFLD had a specific metabolite signature. The plasma metabolite signature was unique for each genetic variant, suggesting that several metabolites and different pathways are involved in the risk of NAFLD. The FLI index reliably identifies metabolites for NAFLD in large population-based studies.<\/jats:p>","DOI":"10.3390\/metabo13020267","type":"journal-article","created":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T02:16:01Z","timestamp":1676340961000},"page":"267","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Plasma Metabolite Signatures in Male Carriers of Genetic Variants Associated with Non-Alcoholic Fatty Liver Disease"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0225-842X","authenticated-orcid":false,"given":"Lilian","family":"Fernandes Silva","sequence":"first","affiliation":[{"name":"Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6657-2659","authenticated-orcid":false,"given":"Jagadish","family":"Vangipurapu","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8866-4482","authenticated-orcid":false,"given":"Anniina","family":"Oravilahti","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ville","family":"M\u00e4nnist\u00f6","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, 70210 Kuopio, Finland"},{"name":"Department of Medicine, Kuopio University Hospital, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3394-7749","authenticated-orcid":false,"given":"Markku","family":"Laakso","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1053\/j.gastro.2014.11.039","article-title":"nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States","volume":"148","author":"Wong","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1002\/hep.26717","article-title":"Extrahepatic complications of nonalcoholic fatty liver disease","volume":"59","author":"Armstrong","year":"2014","journal-title":"Hepatology"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Musso, G., Gambino, R., Tabibian, J.H., Ekstedt, M., Kechagias, S., Hamaguchi, M., Hultcrantz, R., Hagstr\u00f6m, H., Yoon, S.K., and Charatcharoenwitthaya, P. (2014). Association of non-alcoholic fatty liver disease with chronic kidney disease: A systematic review and meta-analysis. PLoS Med., 11.","DOI":"10.1371\/journal.pmed.1001680"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/S2468-1253(21)00020-0","article-title":"Non-alcoholic fatty liver disease: A multisystem disease requiring a multidisciplinary and holistic approach","volume":"6","author":"Targher","year":"2021","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1038\/ng.257","article-title":"Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease","volume":"40","author":"Romeo","year":"2008","journal-title":"Nat. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1002\/hep.23759","article-title":"The association of genetic variability in patatin-like phospholipase domain-containing protein 3 (PNPLA3) with histological severity of nonalcoholic fatty liver disease","volume":"52","author":"Rotman","year":"2010","journal-title":"Hepatology"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Speliotes, E.K., Yerges-Armstrong, L.M., Wu, J., Hernaez, R., Kim, L.J., Palmer, C.D., Gudnason, V., Eiriksdottir, G., Garcia, M.E., and Launer, L.J. (2011). Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet., 7.","DOI":"10.1371\/journal.pgen.1001324"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1002\/hep.27242","article-title":"Pnpla3I148M knock-in mice accumulate PNPLA3 on lipid droplets and develop hepatic steatosis","volume":"61","author":"Smagris","year":"2015","journal-title":"Hepatology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/ng.2901","article-title":"Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease","volume":"46","author":"Kozlitina","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1038\/ng.3417","article-title":"A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis","volume":"47","author":"Buch","year":"2015","journal-title":"Nat Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1053\/j.gastro.2016.01.032","article-title":"The MBOAT7-TMC4 variant rs641738 increases risk of nonalcoholic fatty liver disease in individuals of european descent","volume":"150","author":"Mancina","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1007\/s11033-010-0212-1","article-title":"Genetic variation in the GCKR gene is associated with non-alcoholic fatty liver disease in Chinese people","volume":"38","author":"Yang","year":"2011","journal-title":"Mol. Biol. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1016\/j.cgh.2013.02.011","article-title":"Association between variants in or near PNPLA3, GCKR, and PPP1R3B with ultrasound-defined steatosis based on data from the third national health and nutrition examination survey","volume":"11","author":"Hernaez","year":"2013","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"11437","DOI":"10.1073\/pnas.1410741111","article-title":"Comparative proteomic study reveals 17\u03b2-HSD13 as a pathogenic protein in nonalcoholic fatty liver disease","volume":"111","author":"Su","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.mam.2015.09.002","article-title":"Role of glycogen phosphorylase in liver glycogen metabolism","volume":"46","author":"Agius","year":"2015","journal-title":"Mol. Asp. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1056\/NEJMoa1712191","article-title":"A protein-truncating HSD17B13 variant and protection from chronic liver disease","volume":"378","author":"Cheng","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1111\/j.1572-0241.2000.02046.x","article-title":"Relationship between aminotransferase levels and histopathological findings in patients with nonalcoholic steatohepatitis","volume":"95","author":"Sonsuz","year":"2000","journal-title":"Am. J. Gastroenterol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1002\/hep4.1353","article-title":"Insulin resistance exacerbates genetic predisposition to nonalcoholic fatty liver disease in individuals without diabetes","volume":"3","author":"Barata","year":"2019","journal-title":"Hepatol. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.jhep.2021.10.013","article-title":"Distinct contributions of metabolic dysfunction and genetic risk factors in the pathogenesis of non-alcoholic fatty liver disease","volume":"76","author":"Luukkonen","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Bedogni, G., Kahn, H.S., Bellentani, S., and Tiribelli, C. (2010). A simple index of lipid overaccumulation is a good marker of liver steatosis. BMC Gastroenterol., 10.","DOI":"10.1186\/1471-230X-10-98"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1194\/jlr.O072629","article-title":"The Metabolic Syndrome in Men study: A resource for studies of metabolic and cardiovascular diseases","volume":"58","author":"Laakso","year":"2017","journal-title":"J. Lipid Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.2337\/db08-1607","article-title":"Changes in insulin sensitivity and insulin release in relation to glycemia and glucose tolerance in 6,414 Finnish men","volume":"58","author":"Kuulasmaa","year":"2009","journal-title":"Diabetes"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2013). Diagnosis and classification of diabetes mellitus. Diabetes Care, 36, 67\u201374.","DOI":"10.2337\/dc13-S067"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.2337\/diacare.22.9.1462","article-title":"Insulin sensitivity indices obtained from oral glucose tolerance testing, Comparison with the euglycemic insulin clamp","volume":"22","author":"Matsuda","year":"1999","journal-title":"Diabetes Care"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.2337\/db11-1378","article-title":"Hyperglycemia and a common variant of GCKR are associated with the levels of eight amino acids in 9369 Finnish men","volume":"61","author":"Civelek","year":"2012","journal-title":"Diabetes"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1136\/bmj.296.6631.1238","article-title":"Statistics in medicine, calculating confidence intervals for regression and correlation","volume":"296","author":"Altman","year":"1988","journal-title":"Br. Med. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9521","DOI":"10.1073\/pnas.1901974116","article-title":"Accumulation of PNPLA3 on lipid droplets is the basis of as-sociated hepatic steatosis","volume":"116","author":"BasuRay","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3451","DOI":"10.1093\/hmg\/ddaa162","article-title":"Insights into genetic variants associated with NASH-fibrosis from metabolite profiling","volume":"29","author":"Mann","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1194\/jlr.M034249","article-title":"Disruption of uridine homeostasis links liver pyrimidine metabolism to lipid accumulation","volume":"54","author":"Le","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"D801","DOI":"10.1093\/nar\/gks1065","article-title":"HMDB 3.0-The Human Metabolome Database in 2013","volume":"41","author":"Wishart","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"D603","DOI":"10.1093\/nar\/gkn810","article-title":"HMDB: A knowledgebase for the human metabolome","volume":"37","author":"Wishart","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"D521","DOI":"10.1093\/nar\/gkl923","article-title":"HMDB, the Human Metabolome Database","volume":"35","author":"Wishart","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1002\/jnr.10012","article-title":"3-Ureidopropionate contributes to the neuropathology of 3-ureidopropionase deficiency and severe propionic aciduria: A hypothesis","volume":"66","author":"Okun","year":"2001","journal-title":"J. Neurosci. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1002\/hep.1840380426","article-title":"Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis","volume":"38","author":"Rubio","year":"2003","journal-title":"Hepatology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.1073\/pnas.0536625100","article-title":"Functional pro-teomics of nonalcoholic steatohepatitis, mitochondrial proteins as targets of S-adenosylmethionine","volume":"100","author":"Santamaria","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1097\/MEG.0b013e328345c8c7","article-title":"Elevated hepatic fatty acid oxidation, high plasma fibroblast growth factor 21, and fasting bile acids in nonalcoholic steatohepatitis","volume":"23","author":"Dasarathy","year":"2011","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_37","first-page":"382","article-title":"Metabolomics and lipidomics in NAFLD, biomarkers and non-invasive diagnostic tests","volume":"23","author":"Masoodi","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.jhep.2017.02.014","article-title":"Impaired hepatic lipid synthesis from polyunsaturated fatty acids in TM6SF2 E167K variant carriers with NAFLD","volume":"67","author":"Luukkonen","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Israelsen, M., Juel, H.B., Detlefsen, S., Madsen, B.S., Rasmussen, D.N., Larssn, T.R., Kj\u00e6rgaard, M., Fernandes Jensen, M.J., Stender, S., and Hansen, T. (2022). Metabolic and genetic risk factors are the strongest predictors of Severity of alcohol-related liver fibrosis. Clin. Gastroenterol. Hepatol., 20.","DOI":"10.1016\/j.cgh.2020.11.038"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"S46","DOI":"10.1194\/jlr.R800035-JLR200","article-title":"Recent progress on acyl CoA, lysophospholipid acyltrans-ferase research","volume":"50","author":"Shindou","year":"2009","journal-title":"J. Lipid. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1194\/jlr.P055640","article-title":"Polyunsaturated fatty acid metabolites as novel lipidomic bi-omarkers for noninvasive diagnosis of nonalcoholic steatohepatitis","volume":"56","author":"Loomba","year":"2015","journal-title":"J. Lipid. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e49882","DOI":"10.7554\/eLife.49882","article-title":"Obesity-linked suppression of membrane-bound O-acyltransferase 7 (MBOAT7) drives non-alcoholic fatty liver disease","volume":"8","author":"Helsley","year":"2019","journal-title":"Elife"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1002\/hep.31290","article-title":"The L-\u03b1-Lysophosphatidylinositol\/G Protein-Coupled Receptor 55 System induces the development of nonalcoholic steatosis and steatohepatitis","volume":"73","author":"Fondevila","year":"2021","journal-title":"Hepatology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/S0304-4165(01)00183-0","article-title":"Studies of mannose metabolism and effects of long-term mannose ingestion in the mouse","volume":"1528","author":"Davis","year":"2001","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Gen. Subj."},{"key":"ref_45","first-page":"E534","article-title":"Hepatic glycogen breakdown is implicated in the maintenance of plasma mannose concentration","volume":"288","author":"Taguchi","year":"2005","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.metabol.2010.03.006","article-title":"Plasma metabolomic profile in nonalcoholic fatty liver disease","volume":"60","author":"Kalhan","year":"2011","journal-title":"Metab. Clin. Exp."},{"key":"ref_47","first-page":"1","article-title":"An intronic variant in the GCKR gene is associated with multiple lipids","volume":"9","author":"Silva","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/s41586-020-2337-2","article-title":"Hepatic NADH reductive stress underlies common variation in metabolic traits","volume":"583","author":"Goodman","year":"2020","journal-title":"Nature"},{"key":"ref_49","first-page":"781","article-title":"Pharmacological Nicotinamide, Mechanisms centered around SIRT1 activity","volume":"Volume 10","author":"Hwang","year":"2019","journal-title":"Translational Epigenetics, Pharmacoepigenetics"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s00726-014-1894-9","article-title":"Branched chain amino acid metabolism profiles in progressive human nonalcoholic fatty liver disease","volume":"47","author":"Lake","year":"2015","journal-title":"Amino Acids"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1073\/pnas.67.3.1248","article-title":"The gamma-glutamyl cycle, a possible transport system for amino acids","volume":"67","author":"Orlowski","year":"1970","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"D633","DOI":"10.1093\/nar\/gkx935","article-title":"The MetaCyc database of metabolic pathways and enzymes","volume":"46","author":"Caspi","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1002\/hep4.1077","article-title":"Characteristics of hepatic insulin-sensitive nonalcoholic fatty liver disease","volume":"1","author":"Shigiyama","year":"2017","journal-title":"Hepatol. Commun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1093\/hmg\/ddy067","article-title":"Identification of seven novel loci associated with amino acid levels using single-variant and gene-based tests in 8545 Finnish men from the METSIM study","volume":"27","author":"Teslovich","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1093\/aje\/kwv242","article-title":"Plasma biomarkers of inflammation, the kynurenine pathway, and risks of all-cause, cancer, and cardiovascular disease mortality, The Hordaland Health Study","volume":"183","author":"Zuo","year":"2016","journal-title":"Am. J. Epidemiol."},{"key":"ref_56","first-page":"e132158","article-title":"Hydroxysteroid 17-\u03b2 dehydrogenase 13 variant increases phospholipids and protects against fibrosis in nonalcoholic fatty liver disease","volume":"5","author":"Luukkonen","year":"2020","journal-title":"J. Clin. Investig."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/13\/2\/267\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:34:05Z","timestamp":1760121245000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/13\/2\/267"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,13]]},"references-count":56,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["metabo13020267"],"URL":"https:\/\/doi.org\/10.3390\/metabo13020267","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,13]]}}}