{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T13:01:25Z","timestamp":1792155685108,"version":"4.4.0"},"reference-count":55,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,7,21]],"date-time":"2020-07-21T00:00:00Z","timestamp":1595289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007885","name":"European Association for the Study of Diabetes","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007885","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and aims<\/jats:title><jats:p>Non\u2010alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent and nutrition intervention remains the most important therapeutic approach for NAFLD. Our aim was to investigate whether low\u2010 (LP) or high\u2010protein (HP) diets are more effective in reducing liver fat and reversing NAFLD and which mechanisms are involved.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>19 participants with morbid obesity undergoing bariatric surgery were randomized into two hypocaloric (1500\u20101600\u00a0kcal\/day) diet groups, a low protein (10E% protein) and a high protein (30E% protein), for three weeks prior to surgery. Intrahepatic lipid levels (IHL) and serum fibroblast growth factor 21 (FGF21) were measured before and after the dietary intervention. Autophagy flux, histology, mitochondrial activity and gene expression analyses were performed in liver samples collected during surgery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IHL levels decreased by 42.6% in the HP group, but were not significantly changed in the LP group despite similar weight loss. Hepatic autophagy flux and serum FGF21 increased by 66.7% and 42.2%, respectively, after 3\u00a0weeks in the LP group only. Expression levels of fat uptake and lipid biosynthesis genes were lower in the HP group compared with those in the LP group. RNA\u2010seq analysis revealed lower activity of inflammatory pathways upon HP diet. Hepatic mitochondrial activity and expression of \u03b2\u2010oxidation genes did not increase in the HP group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>HP diet more effectively reduces hepatic fat than LP diet despite of lower autophagy and FGF21. Our data suggest that liver fat reduction upon HP diets result primarily from suppression of fat uptake and lipid biosynthesis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14596","type":"journal-article","created":{"date-parts":[[2020,7,11]],"date-time":"2020-07-11T18:42:54Z","timestamp":1594492974000},"page":"2982-2997","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":77,"title":["High\u2010protein diet more effectively reduces hepatic fat than low\u2010protein diet despite lower autophagy and FGF21 levels"],"prefix":"10.1111","volume":"40","author":[{"given":"Chenchen","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Clinical Nutrition German Institute of Human Nutrition Potsdam\u2010Rehbr\u00fccke (DIfE) Nuthetal Germany"},{"name":"German Center for Diabetes Research (DZD) Munich\u2010Neuherberg Germany"},{"name":"Department of Endocrinology, Diabetes and Nutrition Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariya","family":"Markova","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition German Institute of Human Nutrition Potsdam\u2010Rehbr\u00fccke (DIfE) Nuthetal Germany"},{"name":"German Center for Diabetes Research (DZD) Munich\u2010Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Seebeck","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition German Institute of Human Nutrition Potsdam\u2010Rehbr\u00fccke (DIfE) Nuthetal Germany"},{"name":"German Center for Diabetes Research (DZD) Munich\u2010Neuherberg Germany"},{"name":"Institute of Nutritional Science University of Potsdam Nuthetal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Loft","sequence":"additional","affiliation":[{"name":"German Center for Diabetes Research (DZD) Munich\u2010Neuherberg Germany"},{"name":"Department for Internal Medicine I and Clinical Chemistry Institute for Diabetes and Cancer (IDC) Helmholtz Center Munich Neuherberg and Joint Heidelberg\u2010IDC Translational Diabetes Program Heidelberg University Hospital Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Hornemann","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition German Institute of Human Nutrition Potsdam\u2010Rehbr\u00fccke (DIfE) Nuthetal Germany"},{"name":"German Center for Diabetes Research (DZD) Munich\u2010Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Gantert","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition German Institute of Human Nutrition Potsdam\u2010Rehbr\u00fccke (DIfE) Nuthetal Germany"},{"name":"German Center for Diabetes Research (DZD) Munich\u2010Neuherberg Germany"},{"name":"Institute of Nutritional Science University of Potsdam Nuthetal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kabisch","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition German Institute of Human Nutrition Potsdam\u2010Rehbr\u00fccke (DIfE) Nuthetal Germany"},{"name":"German Center for Diabetes Research (DZD) Munich\u2010Neuherberg Germany"},{"name":"Department of Endocrinology, Diabetes and Nutrition Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Herz","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition German Institute of Human Nutrition Potsdam\u2010Rehbr\u00fccke (DIfE) Nuthetal Germany"},{"name":"German Center for Diabetes Research (DZD) Munich\u2010Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3222-9777","authenticated-orcid":false,"given":"Jennifer","family":"Loske","sequence":"additional","affiliation":[{"name":"Research Group Molecular Nutritional Medicine Department of Molecular Toxicology German Institute of Human Nutrition Potsdam\u2010Rehbruecke Nuthetal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Ost","sequence":"additional","affiliation":[{"name":"Department of Physiology of Energy Metabolism German Institute of Human Nutrition Potsdam\u2010Rehbr\u00fccke (DIfE) Nuthetal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Coleman","sequence":"additional","affiliation":[{"name":"Institute of Nutritional Science University of Potsdam Nuthetal Germany"},{"name":"Department of Physiology of Energy Metabolism German Institute of Human Nutrition Potsdam\u2010Rehbr\u00fccke (DIfE) Nuthetal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick","family":"Klauschen","sequence":"additional","affiliation":[{"name":"Institute of Pathology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"},{"name":"German Cancer Consortium (DKTK) Partner Site Berlin German Cancer Research Center (DKFZ) Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"Clinic for Nutritional Medicine Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Lange","sequence":"additional","affiliation":[{"name":"Centre for Obesity and Metabolic Surgery Vivantes Hospital Berlin Germany"},{"name":"Helios Klinikum Berlin\u2010Buch Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Machann","sequence":"additional","affiliation":[{"name":"German Center for Diabetes Research (DZD) Munich\u2010Neuherberg Germany"},{"name":"Institute of Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich The University of T\u00fcbingen T\u00fcbingen Germany"},{"name":"Section on Experimental Radiology Department of Diagnostic and Interventional Radiology University Hospital T\u00fcbingen T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Klaus","sequence":"additional","affiliation":[{"name":"Institute of Nutritional Science University of Potsdam Nuthetal Germany"},{"name":"Department of Physiology of Energy Metabolism German Institute of Human Nutrition Potsdam\u2010Rehbr\u00fccke (DIfE) Nuthetal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilman","family":"Grune","sequence":"additional","affiliation":[{"name":"German Center for Diabetes Research (DZD) Munich\u2010Neuherberg Germany"},{"name":"Institute of Nutritional Science University of Potsdam Nuthetal Germany"},{"name":"NutriAct\u2010Competence Cluster Nutrition Research Berlin\u2010Potsdam Nuthetal Germany"},{"name":"Department of Molecular Toxicology German Institute of Human Nutrition Potsdam\u2010Rehbruecke (DIfE) Nuthetal Germany"},{"name":"German Center for Cardiovascular Research (DZHK) Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Herzig","sequence":"additional","affiliation":[{"name":"German Center for Diabetes Research (DZD) Munich\u2010Neuherberg Germany"},{"name":"Department for Internal Medicine I and Clinical Chemistry Institute for Diabetes and Cancer (IDC) Helmholtz Center Munich Neuherberg and Joint Heidelberg\u2010IDC Translational Diabetes Program Heidelberg University Hospital Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3583-8546","authenticated-orcid":false,"given":"Olga","family":"Pivovarova\u2010Ramich","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition German Institute of Human Nutrition Potsdam\u2010Rehbr\u00fccke (DIfE) Nuthetal Germany"},{"name":"German Center for Diabetes Research (DZD) Munich\u2010Neuherberg Germany"},{"name":"Department of Endocrinology, Diabetes and Nutrition Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"},{"name":"Research Group Molecular Nutritional Medicine Department of Molecular Toxicology German Institute of Human Nutrition Potsdam\u2010Rehbruecke Nuthetal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas F. H.","family":"Pfeiffer","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition German Institute of Human Nutrition Potsdam\u2010Rehbr\u00fccke (DIfE) Nuthetal Germany"},{"name":"German Center for Diabetes Research (DZD) Munich\u2010Neuherberg Germany"},{"name":"Department of Endocrinology, Diabetes and Nutrition Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2011.04724.x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0000000000000116"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.10.007"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00464-006-9182-8"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2011.01.006"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ctg.2016.28"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85946"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI74915"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.02.009"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.05.007"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-016-2774-2"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2016.02.015"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07976"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.03.039"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3014"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2014.38.4.245"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms15011374"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2011.10.005"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-012-1363-2"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms161226225"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.9.5692"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27173"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2015.03.010"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-1681"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00518.2012"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-382-0_3"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0094689"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-20901-4"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00064.2004"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.232591499"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0109617"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00162.2018"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00926-7"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25151"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040154"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0b013e32833c3026"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.04.004"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.2337\/db13-0501"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2015.05.016"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2009.10.023"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2013.02.003"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-002-0384-9"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2010.10.003"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1017\/S000711451500238X"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012057"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0014664"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00014.2009"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-008-0461-1"},{"issue":"18","key":"e_1_2_10_50_1","doi-asserted-by":"crossref","first-page":"8841","DOI":"10.1016\/S0021-9258(19)86776-5","article-title":"Lysosomal triacylglycerol lipase and lipolysis in isolated rat hepatocytes","volume":"254","author":"Debeer LJ","year":"1979","journal-title":"J Biol Chem"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt563"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-014-1775-2"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20121098"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.04.038"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2019.03.019"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.06.018"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.14596","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/liv.14596","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.14596","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T01:57:02Z","timestamp":1693879022000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.14596"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,21]]},"references-count":55,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["10.1111\/liv.14596"],"URL":"https:\/\/doi.org\/10.1111\/liv.14596","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,21]]},"assertion":[{"value":"2020-04-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}