{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T04:58:30Z","timestamp":1781240310436,"version":"3.54.1"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"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. Immunol."],"abstract":"<jats:p>\n                    Environmental exposure to plasticizer dibutyl phthalate (DBP) is increasingly implicated in skeletal muscle decline, yet the effects and underlying mechanisms remain elusive. This study investigates the impact of DBP on skeletal muscle using a cross-scale integration of epidemiological modeling, computational toxicology, and experimental validations. Mixture modeling of 3,514 NHANES adults (2011\u20132018) demonstrated that combined phthalate exposure negatively correlated with skeletal muscle mass not only in aged but also in young populations. DBP metabolite monobutyl phthalate (MBP) emerged as the predominant toxic driver, mediated by inflammation and oxidative stress (Uric acid to High-density lipoprotein cholesterol Ratio, 20.8%). Phenotypically,\n                    <jats:italic>in vitro<\/jats:italic>\n                    \/\n                    <jats:italic>in vivo<\/jats:italic>\n                    models showed that DBP exposure impairs myogenic differentiation, drives transition from oxidative-glycolytic type IIA fibers toward glycolytic type IIB fibers, and depletes regenerative Pax7\n                    <jats:sup>+<\/jats:sup>\n                    satellite cells, accompanied by myofiber atrophy and lipid infiltration, mirroring environmentally-induced myosteatosis. Mechanistically, systems-level analyses and molecular docking suggest a predictive model wherein DBP\/MBP could act as pseudo-ligands that dock into the active pocket of the primary trigger TNF\u03b1, which specifically upregulates TNFR1 (but not TNFR2), driving dual pathological axes: a proteostatic collapse (ubiquitin-proteasome overactivation and autophagy) and GSDMD-dependent pyroptosis. Pharmacological intervention with Morroniside successfully inhibited TNF\u03b1-driven dual axes, restoring homeostasis and alleviating DBP-induced atrophy. Ultimately, our findings expand the traditional paradigm of sarcopenia beyond age-related decline and nutritional deficits, establishing it additionally as an environmentally-driven metabolic pathology and a pressing public health risk. Furthermore, we redefine phthalate toxicity from generalized endocrine disruption to a targeted, receptor-mediated event driven by the TNF\u03b1\/TNFR1 axis, culminating in environmental sarcopenia.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1853039","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T04:43:03Z","timestamp":1781239383000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dibutyl phthalate induces sarcopenia via TNF\u03b1\/TNFR1-mediated proteolytic and pyroptotic axes: evidence from NHANES and experimental models"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiangjiao","family":"Yi","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Zhejiang Chinese Medical University","place":["Hangzhou, Zhejiang, China"]},{"name":"Center for Biobased Materials, Muyuan Laboratory","place":["Zhengzhou, Henan, China"]},{"name":"The 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