{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T09:35:01Z","timestamp":1786527301250,"version":"build-2736575974"},"reference-count":21,"publisher":"SAGE Publications","issue":"7-9","license":[{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Metabolic-associated fatty liver disease (MASLD) is a leading cause of chronic liver injury worldwide, characterized by hepatic lipid accumulation, oxidative stress, inflammation, and mitochondrial dysfunction. Despite its prevalence, no approved pharmacological treatments currently exist. Atraric acid (AA), a natural compound with antioxidant and anti-inflammatory properties, has not been previously investigated in MASLD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>This study aimed to evaluate the therapeutic potential of AA and elucidate its underlying mechanisms in MASLD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>MASLD was modeled in mice using a high-fat diet and in alpha mouse liver 12 hepatocytes using oleic acid\/palmitic acid. AA\u2019s effects on liver injury, mitochondrial function, and inflammatory signaling were assessed through biochemical assays, histology, transcriptomic analysis, and mechanistic studies involving adenosine 5\u2032-monophosphate-activated protein kinase (AMPK) inhibition and liver-specific AMPK knockout models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      AA significantly improved hepatic steatosis, reduced serum alanine transaminase and aspartate aminotransferase levels, and alleviated inflammation in MASLD mice.\n                      <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                      , AA restored mitochondrial membrane potential, enhanced adenosine triphosphate production, and suppressed reactive oxygen species accumulation and NOD-, LRR-, and pyrin domain-containing protein 3 inflammasome activation. Mechanistically, AA directly interacted with AMPK, promoted its phosphorylation, and upregulated peroxisome proliferator-activated receptor \u03b3 coactivator 1 alpha (PGC-1\u03b1), thereby improving mitochondrial biogenesis and redox balance. These protective effects were abolished by AMPK\u03b1 inhibition or knockout, confirming AMPK as a key mediator. Additionally, AA modulated related pathways, including SIRT1 and mTOR, suggesting broader metabolic benefits.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      AA mitigates MASLD by activating the AMPK\u2013PGC-1\u03b1 axis, restoring mitochondrial function, and reducing ROS-driven inflammation. These findings highlight AA as a promising candidate for MASLD therapy and warrant further clinical investigation.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      44, 332\u2013356.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15230864251406293","type":"journal-article","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T11:52:38Z","timestamp":1767095558000},"page":"332-356","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Atraric Acid Mitigates Mitochondrial Dysfunction and Inflammation via AMPK\u03b1\u2013PGC-1\u03b1 Signaling in Metabolic-Associated Fatty Liver Disease"],"prefix":"10.1177","volume":"44","author":[{"given":"Yannan","family":"Xiang","sequence":"first","affiliation":[{"name":"Institute of Neuroscience, Department of Neurosurgery, Lianyungang Clinical College of Nanjing Medical University, the Affiliated Lianyungang Hospital of Xuzhou Medical University, The First People\u2019s Hospital of Lianyungang, Lianyungang, China."},{"name":"Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihao","family":"Ma","sequence":"additional","affiliation":[{"name":"Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyue","family":"Guan","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Department of Neurosurgery, Lianyungang Clinical College of Nanjing Medical University, the Affiliated Lianyungang Hospital of Xuzhou Medical University, The First People\u2019s Hospital of Lianyungang, Lianyungang, China."},{"name":"Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Huang","sequence":"additional","affiliation":[{"name":"Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinran","family":"Li","sequence":"additional","affiliation":[{"name":"Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihan","family":"Xu","sequence":"additional","affiliation":[{"name":"Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Department of Neurosurgery, Lianyungang Clinical College of Nanjing Medical University, the Affiliated Lianyungang Hospital of Xuzhou Medical University, The First People\u2019s Hospital of Lianyungang, Lianyungang, China."},{"name":"Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Lianyungang Clinical College of Nanjing Medical University, the Affiliated Lianyungang Hospital of Xuzhou Medical University, The First People\u2019s Hospital of Lianyungang, Lianyungang, 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