{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T06:07:11Z","timestamp":1784700431051,"version":"3.55.0"},"reference-count":41,"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. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      This exploratory study aimed to identify the effects of\n                      <jats:italic>SIRT1<\/jats:italic>\n                      polymorphisms on the serum lipidomic profile and pathological characteristics in metabolic dysfunction-associated steatotic liver disease (MASLD).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials<\/jats:title>\n                    <jats:p>\n                      Chinese Han patients with biopsy-proven MASLD were genotyped for the single nucleotide polymorphisms (SNPs) in\n                      <jats:italic>SIRT1<\/jats:italic>\n                      . Lipidomics based on untargeted ultra-performance liquid chromatography\u2013tandem mass spectrometry (UHPLC-MS) was applied to map the\n                      <jats:italic>SIRT1<\/jats:italic>\n                      -driven serum lipid signature, followed by correlation analyses linking these lipid traits to hepatic steatosis, ballooning, lobular inflammation, and fibrosis. Integrative pathological scoring finally explored how\n                      <jats:italic>SIRT1<\/jats:italic>\n                      variants that remodel circulating lipids may be associated with MASLD-specific histological change.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>SIRT1<\/jats:italic>\n                      SNPs (rs3740053, rs2394443, rs2236318, rs7896005, rs2273773, rs2394445, and rs2394446) demonstrated extensive association with serum lipidomics of MASLD patients.\n                      <jats:italic>SIRT1<\/jats:italic>\n                      rs2236318, rs7896005, and rs2394445, affecting 2, 7, and 7 serum triacylglycerols (TAGs) respectively, dominated the\n                      <jats:italic>SIRT1<\/jats:italic>\n                      SNP-lipidomics association. Quantitative analysis revealed significantly elevated TAGs levels (48:0, 50:0, 50:1, 52:0, 52:1, 52:2, and 54:1), the most abundant species, in MASLD patients with rs2394445 A\/A genotype compared with A\/T+T\/T. These elevated rs2394445-dependent TAG levels were associated with high-grade hepatic steatosis (rho: 0.367 to 0.540,\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt;\u202f0.033\u20130.001) rather than ballooning, lobular inflammation, or fibrosis. The significant correlation of rs2394445 A\/A genotype with severe steatosis suggested a potential pathological link through TAG profile modulation. In contrast, rs2394445 showed a limited effect on total circulating lipids and obesity indices (BMI, WHtR).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The A\/A genotype at\n                      <jats:italic>SIRT1<\/jats:italic>\n                      rs2394445 is associated with elevated serum TAGs containing saturated or monounsaturated fatty acids, which are linked to high-grade hepatic steatosis in MASLD independently of obesity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1835298","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:55:51Z","timestamp":1784699751000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["SIRT1 rs2394445 associates with serum triacylglycerol lipidomic profile in metabolic dysfunction-associated steatotic liver disease"],"prefix":"10.3389","volume":"13","author":[{"given":"Qin","family":"Pan","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Xin Hua Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai Institute for Pediatric Research","place":["Shanghai, China"]},{"name":"Department of Gastroenterology & Endoscopy, Xin Hua Hospital, Shanghai Jiao Tong University, School of Medicine","place":["Shanghai, China"]},{"name":"School of Health Science and Engineering, University of Shanghai for Science and Technology","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can-Jie","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Xia","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology & Endoscopy, Xin Hua Hospital, Shanghai Jiao Tong University, School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Dan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Diagnosis and Treatment Center for Liver Diseases, Zheng Xing Hospital","place":["Zhangzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Qiang","family":"Mi","sequence":"additional","affiliation":[{"name":"Department of Infective Diseases, Tian Jin Infectious Disease Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Graduate School, Henan Medical University","place":["Xinxiang, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology & Endoscopy, Xin Hua Hospital, Shanghai Jiao Tong University, School of Medicine","place":["Shanghai, China"]},{"name":"Department of Gastroenterology, Shigatse People\u2019s Hospital","place":["Shigatse, Tibet, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-Yang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tai Zhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University","place":["Linhai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1097\/HEP.0000000000000670","article-title":"Metabolic dysfunction-associated steatotic liver disease: update and impact of 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