{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T06:15:44Z","timestamp":1788156944594,"version":"build-2803163510"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Body mass index (BMI) does not fully characterize heterogeneity in adiposity patterning, lean reserve, and impedance-derived body-composition features. We derived residualized body-composition phenotype axes from routine measurements and examined whether these projected axes provided additional explanatory information for estimated VO\u2082max and alanine aminotransferase (ALT) within BMI strata.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Phenotype axes were derived using principal component analysis (PCA) of six variables (BMI, waist-to-height ratio, fat mass index, fat-free mass index, percent body fat, and phase angle) following residualization for age and sex in 23,698 individuals. Robustness and repeatability were assessed. The derivation-defined axes were externally projected into 5,060 adults aged 20\u201349\u202fyears from the National Health and Nutrition Examination Survey. Survey-weighted regression models were used to examine associations between projected phenotype scores and estimated VO\u2082max from the submaximal treadmill fitness examination (\n                      <jats:italic>n<\/jats:italic>\n                      =\u202f2,721) and alanine aminotransferase (ALT) (\n                      <jats:italic>n<\/jats:italic>\n                      =\u202f4,857) within unified BMI quartile strata, with adjustment for age, sex, and race\/ethnicity. Sensitivity analyses included expanded covariate adjustment, false-discovery-rate correction, interaction testing, protocol-adjusted estimated VO\u2082max models, and ALT clean-sample analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Three axes explained 98.6% of the residualized input variance: PC1 represented a composite body-size\/adiposity axis, PC2 a phase angle-anchored body-composition contrast axis, and PC3 an FFMI-dominant axis. The phenotype structure was robust, repeatable, and structurally concordant in NHANES. Within BMI strata, selected associations with estimated VO\u2082max remained after 24-test BH-FDR correction, including PC2 in Q3 (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      =\u202f1.82, 95% CI 0.41 to 3.22) and PC3 in Q4 (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u202f=\u202f1.72, 95% CI 0.61 to 2.83). For ALT, higher-BMI strata showed divergent PC2 and PC3 associations that remained after BH-FDR correction; for example, in Q4, PC2 was associated with higher ALT (+6.74%, 95% CI 3.23 to 10.38%), whereas PC3 was associated with lower ALT (\u22126.41%, 95% CI\u202f\u2212\u202f10.15% to \u22122.52%). Expanded and endpoint-specific sensitivity analyses were generally consistent with the primary interpretation, although selected associations were attenuated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Projected body-composition phenotype axes derived from six routine measurements provided additional explanatory information for estimated VO\u2082max and ALT within BMI strata. This residualized multivariable framework may help characterize within-BMI heterogeneity in clinical nutrition research, but should not yet be interpreted as a clinical classification or decision-making tool.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1881228","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:40:14Z","timestamp":1788154814000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Body-composition phenotype axes provide additional explanatory information for cardiorespiratory fitness and liver-related metabolic risk within BMI strata"],"prefix":"10.3389","volume":"13","author":[{"given":"Yang","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Clinical Nutrition, West China Hospital, Sichuan University","place":["Chengdu, 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Fan","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Mei","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Yong","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"757","DOI":"10.3390\/ijerph21060757","article-title":"Advantages and limitations of 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