{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T05:02:20Z","timestamp":1789794140902,"version":"4.0.1"},"reference-count":46,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea","award":["RS-2021-NR061667"],"award-info":[{"award-number":["RS-2021-NR061667"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Research Foundation of Korea","award":["RS-2026-25490093"],"award-info":[{"award-number":["RS-2026-25490093"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"crossref"}]},{"award":["RS-2021-NR061667"],"award-info":[{"award-number":["RS-2021-NR061667"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RS-2026-25490093"],"award-info":[{"award-number":["RS-2026-25490093"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Clinical Research Institute of Daejeon St. Mary\u2019s Hospital","award":["CMCDJ-P-2022\u2013020"],"award-info":[{"award-number":["CMCDJ-P-2022\u2013020"]}],"id":[{"id":"https:\/\/ror.org\/01tck1990","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Clinical Research Institute of Daejeon St. Mary\u2019s Hospital","award":["CMCDJ-P-2025-010"],"award-info":[{"award-number":["CMCDJ-P-2025-010"]}],"id":[{"id":"https:\/\/ror.org\/01tck1990","id-type":"ROR","asserted-by":"crossref"}]},{"award":["CMCDJ-P-2022\u2013020"],"award-info":[{"award-number":["CMCDJ-P-2022\u2013020"]}],"id":[{"id":"https:\/\/ror.org\/01tck1990","id-type":"ROR","asserted-by":"publisher"}]},{"award":["CMCDJ-P-2025-010"],"award-info":[{"award-number":["CMCDJ-P-2025-010"]}],"id":[{"id":"https:\/\/ror.org\/01tck1990","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Renal lipotoxicity and oxidative stress are major contributors to diabetic kidney disease (DKD), but the role of proprotein convertase subtilisin\/kexin type 9 (PCSK9) and its relationship with AMP-activated protein kinase (AMPK) signaling remain unclear. We investigated the effects of PCSK9 inhibition on renal lipotoxicity and oxidative stress in db\/db mice and high-glucose (HG)-treated HK-2 cells using a selective PCSK9 inhibitor (PCSK9i) with or without AMPK\u03b11\/\u03b12 small interfering RNA (siRNA). PCSK9i significantly reduced albuminuria, renal injury, histopathological changes, and intrarenal lipid accumulation without altering glycemic control. These effects were accompanied by increased low-density lipoprotein receptor (LDLR) expression, reduced cluster of differentiation 36 (CD36) expression, enhanced AMPK phosphorylation and peroxisome proliferator-activated receptor gamma coactivator-1\u03b1 (PGC-1\u03b1) expression, reduced sterol regulatory element-binding protein-1c (SREBP-1c) expression, restored carnitine palmitoyltransferase 1 (CPT1) expression, modulated protein kinase B (Akt)\/forkhead box O (FoxO) signaling, and reduced oxidative stress and apoptosis. Similar findings were observed in HG-treated HK-2 cells. Importantly, AMPK knockdown attenuated the protective effects of PCSK9i on lipid metabolism, oxidative stress, and apoptosis in HK-2 cells. PCSK9 inhibition attenuates renal lipotoxicity and oxidative stress in DKD, providing a preclinical rationale for further investigation of the renal metabolic effects of PCSK9-directed therapies and their association with AMPK activation.<\/jats:p>","DOI":"10.3390\/antiox15091182","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T09:59:03Z","timestamp":1789639143000},"page":"1182","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PCSK9 Inhibition Attenuates Renal Oxidative Stress and Lipotoxicity in Diabetic Kidney Disease in Association with AMPK Activation"],"prefix":"10.3390","volume":"15","author":[{"given":"Keum-Jin","family":"Yang","sequence":"first","affiliation":[{"name":"Clinical Research Institute, Daejeon St. Mary\u2019s Hospital, Daejeon 34943, Republic of 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Nephrology, Department of Internal Medicine, Bucheon St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Hwajin","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Daejeon St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Yunkyeong","family":"Hwang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Daejeon St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of 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Whee","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7856-4955","authenticated-orcid":false,"given":"Yu Ah","family":"Hong","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Daejeon St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of 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