{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T20:23:43Z","timestamp":1787689423147,"version":"build-2784847793"},"reference-count":41,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"American Cancer Society Research Scholar"},{"name":"American Cancer Society Interdisciplinary Team","award":["PASD-22\u20131003396"],"award-info":[{"award-number":["PASD-22\u20131003396"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Obesity increases risks of chronic liver disease and liver cancer, but risks across obesity phenotypes and related molecular signatures remain incompletely characterized. We evaluated associations of obesity phenotypes and obesity-related omics signatures with adverse liver outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed 451\u2009463 UK Biobank participants aged 40-69\u2009years. General and central obesity were defined by body mass index and waist circumference. Metabolically unhealthy obesity was defined as obesity plus at least 1 metabolic abnormality. Liver outcomes (metabolic dysfunction\u2013associated steatotic liver disease, cirrhosis, liver cancer, severe liver disease, and chronic liver disease mortality) were ascertained from hospital inpatient records, cancer and death registries. Cox models estimated hazard ratios (HRs) for obesity measures, and internally validated nuclear magnetic resonance metabolomic and Olink proteomic signatures were derived using elastic-net regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>During a median 11-year follow-up, general obesity and central obesity were associated with higher risks of adverse liver outcomes (HR = 1.53-3.29), with generally stronger associations for metabolically unhealthy obesity (HR = 1.69-3.68). Participants with both general and central obesity had the highest risks. Omics signatures of metabolically unhealthy obesity were more strongly associated with liver outcomes than general or central obesity signatures (HR = 1.58-6.13 vs 1.43-4.72). Nuclear magnetic resonance metabolomic biomarkers (albumin, glutamine, triglycerides) and proteomic biomarkers (FABP4, CDHR2, TGFBR2, IL1RN) were consistently associated with multiple liver outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Obesity phenotypes, particularly metabolically unhealthy obesity, and obesity-related omics signatures were associated with higher risks of liver cancer and other adverse liver outcomes. Findings highlight metabolic dysfunction beyond adiposity as an important dimension of obesity-related liver risk and suggest that metabolomic and proteomic profiles may provide molecular insight.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jnci\/djag242","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T11:43:38Z","timestamp":1784288618000},"source":"Crossref","is-referenced-by-count":0,"title":["Obesity phenotypes, omics signatures, and risk of adverse liver outcomes"],"prefix":"10.1093","author":[{"given":"Longgang","family":"Zhao","sequence":"first","affiliation":[{"name":"Yale School of Nursing , Orange, CT,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2516-0946","authenticated-orcid":false,"given":"Yun","family":"Chen","sequence":"additional","affiliation":[{"name":"Yale School of Nursing , Orange, CT,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Harvard T.H. 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