{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:18:41Z","timestamp":1790403521392,"version":"4.1.0"},"reference-count":40,"publisher":"American Diabetes Association","issue":"8","license":[{"start":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:00:00Z","timestamp":1630108800000},"content-version":"vor","delay-in-days":2970,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,8,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>Nonalcoholic fatty liver (NAFL) is thought to contribute to insulin resistance and its metabolic complications. However, some individuals with NAFL remain insulin sensitive. Mechanisms involved in the susceptibility to develop insulin resistance in humans with NAFL are largely unknown. We investigated circulating markers and mechanisms of a metabolically benign and malignant NAFL by applying a metabolomic approach.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>A total of 265 metabolites were analyzed before and after a 9-month lifestyle intervention in plasma from 20 insulin-sensitive and 20 insulin-resistant subjects with NAFL. The relevant plasma metabolites were then tested for relationships with insulin sensitivity in 17 subjects without NAFL and in plasma from 29 subjects with liver tissue samples.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>The best separation of the insulin-sensitive from the insulin-resistant NAFL group was achieved by a metabolite pattern including the branched-chain amino acids leucine and isoleucine, ornithine, the acylcarnitines C3:0-, C16:0-, and C18:0-carnitine, and lysophosphatidylcholine (lyso-PC) C16:0 (area under the ROC curve, 0.77 [P = 0.00023] at baseline and 0.80 [P = 0.000019] at follow-up). Among the individual metabolites, predominantly higher levels of lyso-PC C16:0, both at baseline (P = 0.0039) and at follow-up (P = 0.001), were found in the insulin-sensitive compared with the insulin-resistant subjects. In the non-NAFL groups, no differences in lyso-PC C16:0 levels were found between the insulin-sensitive and insulin-resistant subjects, and these relationships were replicated in plasma from subjects with liver tissue samples.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>From a plasma metabolomic pattern, particularly lyso-PCs are able to separate metabolically benign from malignant NAFL in humans and may highlight important pathways in the pathogenesis of fatty liver\u2013induced insulin resistance.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc12-1760","type":"journal-article","created":{"date-parts":[[2013,3,21]],"date-time":"2013-03-21T05:43:06Z","timestamp":1363844586000},"page":"2331-2338","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":105,"title":["Circulating Lysophosphatidylcholines Are Markers of a Metabolically Benign Nonalcoholic Fatty Liver"],"prefix":"10.2337","volume":"36","author":[{"given":"Rainer","family":"Lehmann","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology, and Clinical Chemistry, Department of Internal Medicine, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"Institute of Diabetes Research and Metabolic Diseases, Member of the German Center for Diabetes Research, University of T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Franken","sequence":"additional","affiliation":[{"name":"Center for Bioinformatics, University of Tuebingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha","family":"Dammeier","sequence":"additional","affiliation":[{"name":"Medical Proteome Center, Institute for Ophthalmic Research, University of T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Rosenbaum","sequence":"additional","affiliation":[{"name":"Center for Bioinformatics, University of Tuebingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Kantartzis","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology, and Clinical Chemistry, Department of Internal Medicine, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"Institute of Diabetes Research and Metabolic Diseases, Member of the German Center for Diabetes Research, University of T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Peter","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology, and Clinical Chemistry, Department of Internal Medicine, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"Institute of Diabetes Research and Metabolic Diseases, Member of the German Center for Diabetes Research, University of T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Zell","sequence":"additional","affiliation":[{"name":"Center for Bioinformatics, University of Tuebingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Adam","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University of T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Li","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwin","family":"Schleicher","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology, and Clinical Chemistry, Department of Internal Medicine, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"Institute of Diabetes Research and Metabolic Diseases, Member of the German Center for Diabetes Research, University of T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia","family":"Gastaldelli","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, National Research Council, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Fritsche","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology, and Clinical Chemistry, Department of Internal Medicine, 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