{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T21:10:37Z","timestamp":1786396237162,"version":"build-2736575974"},"reference-count":56,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,5,20]]},"abstract":"<jats:sec id=\"jah310825-sec-0001\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Weight reduction through lifestyle, activity, and dietary interventions are the mainstay of initial therapy for metabolic dysfunction associated steatotic liver disease. Data on the relative effectiveness and metabolic pathways linking weight loss and decreased hepatic steatosis are lacking. We sought to identify coordinated changes between the circulating proteome and hepatic steatosis within a randomized clinical trial of alternate day fasting and exercise and prioritize proteins relevant to hepatic steatosis within a broader context using a community cohort.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec id=\"jah310825-sec-0002\" xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We quantified a broad cardiometabolic proteome (&gt;300 proteins) in 67 individuals randomized in a 2\u00d72 factorial design to alternate day fasting and exercise before and after the 3\u2010month intervention to identify proteomic signatures of hepatic steatosis (measured by magnetic resonance imaging proton density fat fraction). Then, we analyzed the cross\u2010sectional relationship of overlapping proteins (\u2248170) with hepatic attenuation (a computed tomographic technique linked to steatosis) in 707 participants from a community cohort. Principal component analysis demonstrated a proteomic signature associated with intrahepatic triglyceride content (Spearman rho=0.55,\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              &lt;0.001) and insulin resistance (homeostatic model assessment for insulin resistance, Spearman rho=0.39,\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              =0.001). Changes in this proteomic signature were associated with changes in intrahepatic triglyceride content over the intervention period (beta=0.12,\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              &lt;0.001). Moreover, cross\u2010sectional analysis of overlapping proteins with hepatic attenuation in the community cohort showed generally, directionally consistent associations with hepatic steatosis.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec id=\"jah310825-sec-0003\" xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">These findings highlight the potential for broad proteomic profiling in small nutritional interventional studies with serial phenotyping alongside confirmatory large cohort epidemiology to prioritize targets of hepatic steatosis and cardiometabolic risk for mechanistic study.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.124.037100","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T09:25:05Z","timestamp":1747301105000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Circulating Proteomics Identifies a Dynamic Profile of Hepatic Steatosis During Metabolic Intervention"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5252-4293","authenticated-orcid":false,"given":"Bassim","family":"El\u2010Sabawi","sequence":"first","affiliation":[{"name":"Vanderbilt University School of Medicine","place":["Nashville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1491-8803","authenticated-orcid":false,"given":"Kahraman","family":"Tanriverdi","sequence":"additional","affiliation":[{"name":"Vanderbilt University School of Medicine","place":["Nashville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2693-1578","authenticated-orcid":false,"given":"Priya","family":"Gajjar","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine","place":["Boston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6993-9396","authenticated-orcid":false,"given":"Matthew","family":"Nayor","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine","place":["Boston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2431-6053","authenticated-orcid":false,"given":"Joshua M.","family":"Landman","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center","place":["Nashville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1346-1872","authenticated-orcid":false,"given":"Jennifer E.","family":"Below","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center","place":["Nashville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine","family":"Haff","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine","place":["Boston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6131-3981","authenticated-orcid":false,"given":"Michelle","family":"Long","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine","place":["Boston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0746-2414","authenticated-orcid":false,"given":"Mark","family":"Ezpeleta","sequence":"additional","affiliation":[{"name":"University of Illinois at Chicago","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0011-6164","authenticated-orcid":false,"given":"Jane E.","family":"Freedman","sequence":"additional","affiliation":[{"name":"Vanderbilt University School of Medicine","place":["Nashville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krista","family":"Varady","sequence":"additional","affiliation":[{"name":"University of Illinois at Chicago","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4471-7156","authenticated-orcid":false,"given":"Ravi","family":"Shah","sequence":"additional","affiliation":[{"name":"Vanderbilt University School of Medicine","place":["Nashville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3342-6158","authenticated-orcid":false,"given":"Andrew S.","family":"Perry","sequence":"additional","affiliation":[{"name":"Vanderbilt University School of Medicine","place":["Nashville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28431"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2015.09.017"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2023.08.005"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.2147\/dmso.s426102"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2032183"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.05.016"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2022.3050"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2020.4153"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abd8034"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.12.001"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-019-06072-4"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a112813"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.119.006749"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2021204288"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2018.11.037"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.124.320737"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.13464"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01199-5"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa792"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1177\/0300060520935219"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.120.315365"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-79948-x"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0803189"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-022-01637-7"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.06.031"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1177\/1756284818815184"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1097\/mbc.0000000000000009"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2021.08.002"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.11.029"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci143690"},{"key":"e_1_3_1_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.03.013"},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-009-9309-8"},{"key":"e_1_3_1_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14857"},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2020.11249"},{"key":"e_1_3_1_36_2","doi-asserted-by":"publisher","DOI":"10.1080\/10799893.2020.1726952"},{"key":"e_1_3_1_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31713"},{"key":"e_1_3_1_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2015.08.004"},{"key":"e_1_3_1_39_2","doi-asserted-by":"publisher","DOI":"10.15252\/msb.20188793"},{"key":"e_1_3_1_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.12.148"},{"key":"e_1_3_1_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.03.008"},{"key":"e_1_3_1_42_2","doi-asserted-by":"publisher","DOI":"10.2147\/ott.S97367"},{"key":"e_1_3_1_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-01663-y"},{"key":"e_1_3_1_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2014.07.017"},{"key":"e_1_3_1_45_2","doi-asserted-by":"publisher","DOI":"10.2174\/157436211795659955"},{"key":"e_1_3_1_46_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu12051476"},{"key":"e_1_3_1_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-64636-7"},{"key":"e_1_3_1_48_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.9b00090"},{"key":"e_1_3_1_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcpro.2023.100601"},{"key":"e_1_3_1_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-021-00400-z"},{"key":"e_1_3_1_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjms.2023.11.007"},{"key":"e_1_3_1_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14063"},{"key":"e_1_3_1_53_2","doi-asserted-by":"publisher","DOI":"10.1139\/apnm-2019-0554"},{"key":"e_1_3_1_54_2","doi-asserted-by":"publisher","DOI":"10.1002\/oby.23579"},{"key":"e_1_3_1_55_2","doi-asserted-by":"publisher","DOI":"10.1002\/oby.22564"},{"key":"e_1_3_1_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2017.11.018"},{"key":"e_1_3_1_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.07.016"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.124.037100","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T12:05:26Z","timestamp":1747742726000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.124.037100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,20]]},"references-count":56,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,5,20]]}},"alternative-id":["10.1161\/JAHA.124.037100"],"URL":"https:\/\/doi.org\/10.1161\/jaha.124.037100","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,20]]},"assertion":[{"value":"2024-06-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e037100"}}