{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T23:54:37Z","timestamp":1774569277732,"version":"3.50.1"},"reference-count":52,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FASEB BioAdvances"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Heat stroke (HS) is the most severe form of hyperthermia, with mortality exceeding 50% in severe cases. The liver is highly vulnerable to HS\u2010induced injury, often triggering multi\u2010organ failure. Although rapid cooling remains the primary treatment, the molecular mechanisms underlying hepatic damage remain elusive, highlighting an urgent need for mechanistic insights, especially given global extreme heat events. We established a HS model by gradually increasing the core temperature of mice from 40\u00b0C to 43\u00b0C. Mice were sacrificed at each target temperature to collect blood and liver tissues for hematological, biochemical, and histopathological analyses. Transcriptomic profiling was conducted on murine livers, and differentially expressed genes (DEGs) were identified and analyzed. The peroxisome proliferator\u2010activated receptor (PPAR) signaling pathway was identified as a significantly enriched pathway and 12 key DEGs were validated by reverse transcription quantitative PCR (RT\u2010qPCR) to assess temperature\u2010dependent metabolic reprogramming. The expression of CD36, ACOX3, and PPAR\u03b1 was validated by immunohistochemistry at the protein level to investigate their response to heat stress. A graded murine HS model was established and histopathology analysis showed significant liver injury with core temperatures \u2265\u200942\u00b0C, manifesting as weight loss, elevated serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), neutrophilia, thrombocytopenia, hepatocyte necrosis, and sinusoidal congestion. Transcriptomic profiling revealed temperature\u2010dependent DEGs from 41\u00b0C onward mainly involved in inflammatory\/immune, lipid metabolism, apoptosis, and stress response pathways. DEGs consistently dysregulated across different temperatures were enriched in PPAR, insulin signaling, and endoplasmic reticulum (ER) stress\u2010related pathways. RT\u2010qPCR analysis revealed the altered expression of PPAR\u2010related key genes, indicating functional disruption in lipid metabolism. Immunohistochemistry further confirmed these transcriptomic findings at the protein level, suggesting that heat stress induced reprogramming of the PPAR signaling pathway. Together, these findings suggest that HS\u2010induced liver injury is closely associated with progressive metabolic reprogramming, with dysregulated lipid metabolism playing a central pathogenic role. By combining a murine stepwise HS model and transcriptomic analysis, we identified dysregulated PPAR signaling as a key temperature\u2010dependent feature of liver injury, suggesting its potential role as a temperature\u2010sensing node and therapeutic target. This work provides a framework with precise temporal windows and molecular candidates for the development of mechanism\u2010directed intervention strategies for HS.<\/jats:p>","DOI":"10.1096\/fba.2025-00308","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T06:09:34Z","timestamp":1774418974000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Temperature\u2010Gradient Transcriptomic Atlas Reveals the\n                    <scp>PPAR<\/scp>\n                    Signaling Pathway Dysfunction in Heat Stroke Induced Liver Injury"],"prefix":"10.1096","volume":"8","author":[{"given":"Ying","family":"Zhu","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences Anhui Medical University  Hefei China"},{"name":"State Key Laboratory of Medical Proteomics National Center for Protein Sciences (Beijing)  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4116-2597","authenticated-orcid":false,"given":"Wanlin","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Proteomics National Center for Protein Sciences (Beijing)  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunyuan","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Proteomics National Center for Protein Sciences (Beijing)  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teng","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Anhui Medical University  Hefei China"},{"name":"State Key Laboratory of Medical Proteomics National Center for Protein Sciences (Beijing)  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingfei","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Proteomics National Center for Protein Sciences (Beijing)  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinxu","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Proteomics National Center for Protein Sciences (Beijing)  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunping","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Anhui Medical University  Hefei China"},{"name":"State Key Laboratory of Medical Proteomics National Center for Protein Sciences (Beijing)  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8934-922X","authenticated-orcid":false,"given":"Jie","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Proteomics National Center for Protein Sciences (Beijing)  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00334-6"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1810762"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40560-018-0298-4"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjmed-2022-000239"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/OAEM.S419028"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)01208-3"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2542-5196(21)00081-4"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02419-z"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra011089"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/burnst\/tkae050"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102409"},{"issue":"11","key":"e_1_2_14_13_1","first-page":"1325","article-title":"Heat\u2010Related Illness","volume":"83","author":"Becker J. 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