{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T12:01:59Z","timestamp":1784721719981,"version":"3.55.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Hashimoto's thyroiditis (HT) is a prevalent autoimmune thyroid disorder, typically triggers localized thyroid inflammation and systemic dyslipidemia, and progression to hypothyroidism. While growth differentiation factor 15 (GDF15) is recognized for its role in lipid metabolism and inflammatory diseases, its specific involvement in HT remains elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted plasma metabolomic profiling in HT patients and matched healthy controls to identify altered metabolic pathways. Correlation analysis was performed between serum GDF15 and clinical indicators. In vitro thyroid follicular cell models and NaI-induced in vivo thyroid inflammatory models were applied with GDF15 overexpression, knockdown, recombinant protein and siRNA treatment to explore the functional role of GDF15.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Plasma metabolomic profiling in HT patients revealed that differentially expressed metabolites are predominantly enriched in lipid metabolism pathways. GDF15 expression was increased by 1.98-fold in HT serum compared to controls (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001), and serum GDF15 levels were negatively correlated with thyroid-stimulating hormone (TSH,\n                      <jats:italic>R<\/jats:italic>\n                      = \u22120.4943,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0040), aspartate aminotransferase (AST,\n                      <jats:italic>R<\/jats:italic>\n                      = \u22120.4506,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0238) and ultrasound attenuation parameter (UAP,\n                      <jats:italic>R<\/jats:italic>\n                      = \u22120.4894,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0071) in HT patients. Functional assays demonstrated that GDF15 overexpression tends to attenuate NaI-induced thyroid and systemic inflammation, relatively improving lipid profiles and reduces hepatic lipid deposition; however, GDF15 knockdown appeared to exacerbate these pathologies. Furthermore, recombinant GDF15 protein mitigates NaI-induced inflammatory responses in thyroid follicular cells, whereas\n                      <jats:italic>GDF15<\/jats:italic>\n                      siRNA intensifies the inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Given the limitations of the NaI-induced model and the lack of thyroid-specific genetic manipulation, these findings suggest a significant association between GDF15 and HT, though further research is required to establish definitive causality.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1854594","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T11:10:19Z","timestamp":1784718619000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Thyroid follicular cell-derived GDF15 attenuates inflammation and lipid dysregulation in Hashimoto's thyroiditis"],"prefix":"10.3389","volume":"13","author":[{"given":"Ruili","family":"Yin","sequence":"first","affiliation":[{"name":"Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University","place":["Beijing, China"]},{"name":"Department of Endocrinology and Metabolism, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongxin","family":"Sun","sequence":"additional","affiliation":[{"name":"Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boshen","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyan","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"918","DOI":"10.3390\/cells12060918","article-title":"Molecular mechanisms in 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