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Low thyroid hormone (T\n                      <jats:sub>3<\/jats:sub>\n                      ) levels are linked to a higher risk of developing metabolic dysfunction\u2010associated steatotic liver disease (MASLD). Epidemiological studies have confirmed the positive correlation between hypothyroidism and MASLD. Unraveling the molecular mechanisms of T\n                      <jats:sub>3<\/jats:sub>\n                      signaling pathways in MASLD will enhance the prospects of identifying effective and specific targets. Therefore, this review discusses the significant role of thyroid hormones in the homeostasis of fat metabolism and describes the possible molecular mechanisms of thyromimetics in the treatment of MASLD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A comprehensive search in PubMed and EMBASE was conducted using the keywords \u201cthyromimetics and liver diseases,\u201d \u201cthyroid hormone and liver diseases,\u201d \u201chypothyroidism and liver diseases,\u201d \u201cT\n                      <jats:sub>3<\/jats:sub>\n                      , T\n                      <jats:sub>4<\/jats:sub>\n                      and liver disease,\u201d and \u201cresmetirom and liver disease.\u201d Relevant papers published before October 2024 were included.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      T\n                      <jats:sub>3<\/jats:sub>\n                      treatment enhances mitochondrial respiration, biogenesis, \u03b2\u2010oxidation, and mitophagy, reducing liver lipid accumulation. However, T\n                      <jats:sub>3<\/jats:sub>\n                      treatment causes cardiotoxicity through thyroid hormone receptor (THR)\u03b1 agonistic activity. To address this, molecules with high THR\u03b2 agonistic but lower THR\u03b1 activity have been developed. Besides resmetirom, other THR\u03b2 agonists like TG68, CS27109, MB07811, and KB\u2010141 show promising results in experimental studies. These molecules upregulate THR\u03b2 target genes, activate genes for fatty acid \u03b2\u2010oxidation in mitochondria and fatty acid breakdown in peroxisomes, downregulate the genes involved in de novo lipogenesis, reduce inflammation by downregulating NF\u2010\u03baB\/JNK\/STAT3 signaling pathways, and accelerate fibrosis resolution by downregulating the expressions of fibrosis marker genes in NASH liver tissue.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Future clinical studies should thoroughly investigate THR\u03b2 agonists, including TG68, CS27109, MB07811, and KB\u2010141.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jgh.16874","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T05:58:46Z","timestamp":1737007126000},"page":"367-378","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Thyromimetics and MASLD: Unveiling the Novel Molecules Beyond Resmetirom"],"prefix":"10.1111","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5068-2383","authenticated-orcid":false,"given":"Devaraj","family":"Ezhilarasan","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Hepatology and Molecular Medicine Lab Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS)  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.7861\/clinmedicine.18-3-245"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12902-022-00980-1"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.34172\/mejdd.2022.270"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2024.155912"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hbpd.2022.10.003"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2022.103902"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17050774"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(98)70599-2"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.113869"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2015.12.012"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.109"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2024.02.007"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2024.155999"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2017.08.003"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/lt.25657"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.03.017"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-024-00986-0"},{"issue":"2","key":"e_1_2_10_19_1","first-page":"158","article-title":"Hormone\u2010Based Pharmacotherapy for Metabolic Dysfunction\u2010Associated Fatty Liver Disease","volume":"4","author":"Chui Z. 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