{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,10]],"date-time":"2025-05-10T19:40:07Z","timestamp":1746906007844,"version":"3.40.5"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,10]],"date-time":"2025-05-10T00:00:00Z","timestamp":1746835200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,5,10]],"date-time":"2025-05-10T00:00:00Z","timestamp":1746835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81871132"],"award-info":[{"award-number":["81871132"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Lipids Health Dis"],"DOI":"10.1186\/s12944-025-02575-w","type":"journal-article","created":{"date-parts":[[2025,5,10]],"date-time":"2025-05-10T06:05:00Z","timestamp":1746857100000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Decreased protein activator of interferon induced protein kinase (PRKRA) involved in menopause-related cholesterol metabolic disorders by regulating cholesterol biosynthesis"],"prefix":"10.1186","volume":"24","author":[{"given":"Le","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanting","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sa","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shien","family":"Zou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,5,10]]},"reference":[{"key":"2575_CR1","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1210\/jc.2011-3362","volume":"97","author":"SD Harlow","year":"2012","unstructured":"Harlow SD, Gass M, Hall JE, Lobo R, Maki P, Rebar RW, et al. Executive summary of the stages of reproductive aging Workshop\u2009+\u200910: addressing the unfinished agenda of staging reproductive aging. J Clin Endocrinol Metab. 2012;97:1159\u201368.","journal-title":"J Clin Endocrinol Metab"},{"key":"2575_CR2","doi-asserted-by":"publisher","first-page":"101109","DOI":"10.1016\/j.plipres.2021.101109","volume":"83","author":"H Li","year":"2021","unstructured":"Li H, Yu X-H, Ou X, Ouyang X-P, Tang C-K. Hepatic cholesterol transport and its role in non-alcoholic fatty liver disease and atherosclerosis. Prog Lipid Res. 2021;83:101109.","journal-title":"Prog Lipid Res"},{"key":"2575_CR3","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.maturitas.2023.02.004","volume":"171","author":"A Armeni","year":"2023","unstructured":"Armeni A, Anagnostis P, Armeni E, Mili N, Goulis D, Lambrinoudaki I. Vasomotor symptoms and risk of cardiovascular disease in peri- and postmenopausal women: A systematic review and meta-analysis. Maturitas. 2023;171:13\u201320.","journal-title":"Maturitas"},{"key":"2575_CR4","doi-asserted-by":"publisher","first-page":"2411","DOI":"10.1001\/jama.2019.19191","volume":"322","author":"MC Honigberg","year":"2019","unstructured":"Honigberg MC, Zekavat SM, Aragam K, Finneran P, Klarin D, Bhatt DL, et al. Association of premature natural and surgical menopause with incident cardiovascular disease. JAMA. 2019;322:2411\u201321.","journal-title":"JAMA"},{"key":"2575_CR5","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.maturitas.2021.06.012","volume":"151","author":"R Robeva","year":"2021","unstructured":"Robeva R, Mladenovi\u0107 D, Veskovi\u0107 M, Hrn\u010di\u0107 D, Bjeki\u0107-Macut J, Stanojlovi\u0107 O, et al. The interplay between metabolic dysregulations and non-alcoholic fatty liver disease in women after menopause. Maturitas. 2021;151:22\u201330.","journal-title":"Maturitas"},{"key":"2575_CR6","doi-asserted-by":"publisher","first-page":"202","DOI":"10.3390\/nu12010202","volume":"12","author":"S-H Ko","year":"2020","unstructured":"Ko S-H, Kim H-S. Menopause-Associated lipid metabolic disorders and foods beneficial for postmenopausal women. Nutrients. 2020;12:202.","journal-title":"Nutrients"},{"key":"2575_CR7","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.bpobgyn.2022.03.003","volume":"81","author":"V Talaulikar","year":"2022","unstructured":"Talaulikar V. Menopause transition: physiology and symptoms. Best Pract Res Clin Obstet Gynaecol. 2022;81:3\u20137.","journal-title":"Best Pract Res Clin Obstet Gynaecol"},{"key":"2575_CR8","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1001\/jama.288.3.321","volume":"288","author":"JE Rossouw","year":"2002","unstructured":"Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of Estrogen plus progestin in healthy postmenopausal women: principal results from the women\u2019s health initiative randomized controlled trial. JAMA. 2002;288:321\u201333.","journal-title":"JAMA"},{"key":"2575_CR9","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s11658-019-0194-5","volume":"24","author":"Y Meng","year":"2019","unstructured":"Meng Y, Zong L. Estrogen stimulates SREBP2 expression in hepatic cell lines via an Estrogen response element in the SREBP2 promoter. Cell Mol Biol Lett. 2019;24:65.","journal-title":"Cell Mol Biol Lett"},{"key":"2575_CR10","unstructured":"Y G, M Z, T B, S M, Z Y, W C, et al. Blocking FSH inhibits hepatic cholesterol biosynthesis and reduces serum cholesterol. Cell research [Internet]. 2019 [cited 2023 Sep 19];29. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/30559440\/"},{"key":"2575_CR11","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1038\/s41467-023-36681-z","volume":"14","author":"S Qiao","year":"2023","unstructured":"Qiao S, Alasmi S, Wyatt A, Wartenberg P, Wang H, Candlish M, et al. Intra-pituitary follicle-stimulating hormone signaling regulates hepatic lipid metabolism in mice. Nat Commun. 2023;14:1098.","journal-title":"Nat Commun"},{"key":"2575_CR12","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1038\/s41419-022-04752-6","volume":"13","author":"M-Y Ou","year":"2022","unstructured":"Ou M-Y, Zhang H, Tan P-C, Zhou S-B, Li Q-F. Adipose tissue aging: mechanisms and therapeutic implications. Cell Death Dis. 2022;13:300.","journal-title":"Cell Death Dis"},{"key":"2575_CR13","first-page":"9","volume":"32","author":"MB Stout","year":"2017","unstructured":"Stout MB, Justice JN, Nicklas BJ, Kirkland JL. Physiological aging: links among adipose tissue dysfunction, diabetes, and frailty. Physiol (Bethesda). 2017;32:9\u201319.","journal-title":"Physiol (Bethesda)"},{"key":"2575_CR14","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1016\/S0140-6736(08)60346-3","volume":"371","author":"HD Nelson","year":"2008","unstructured":"Nelson HD. Menopause Lancet. 2008;371:760\u201370.","journal-title":"Menopause Lancet"},{"key":"2575_CR15","doi-asserted-by":"publisher","first-page":"4379","DOI":"10.1093\/emboj\/17.15.4379","volume":"17","author":"RC Patel","year":"1998","unstructured":"Patel RC, Sen GC. PACT, is a protein activator of the interferon-induced protein kinase, PKR. EMBO J. 1998;17:4379\u201390.","journal-title":"EMBO J"},{"key":"2575_CR16","doi-asserted-by":"publisher","first-page":"37993","DOI":"10.1074\/jbc.M004762200","volume":"275","author":"CV Patel","year":"2000","unstructured":"Patel CV, Handy I, Goldsmith T, Patel RC. PACT, a stress-modulated cellular activator of interferon-induced double-stranded RNA-activated protein kinase, PKR. J Biol Chem. 2000;275:37993\u20138.","journal-title":"J Biol Chem"},{"key":"2575_CR17","doi-asserted-by":"publisher","first-page":"6365","DOI":"10.1111\/febs.15691","volume":"288","author":"E Chukwurah","year":"2021","unstructured":"Chukwurah E, Farabaugh KT, Guan B-J, Ramakrishnan P, Hatzoglou M. A Tale of two proteins: PACT and PKR and their roles in inflammation. FEBS J. 2021;288:6365\u201391.","journal-title":"FEBS J"},{"key":"2575_CR18","doi-asserted-by":"publisher","first-page":"e17194","DOI":"10.1016\/j.heliyon.2023.e17194","volume":"9","author":"J Qiu","year":"2023","unstructured":"Qiu J, Feng M, Yang G, Su D, Zhao F, Liu Y, et al. PRKRA promotes pancreatic cancer progression by upregulating MMP1 transcription via the NF-\u03baB pathway. Heliyon. 2023;9:e17194.","journal-title":"Heliyon"},{"key":"2575_CR19","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1158\/1535-7163.MCT-17-1050","volume":"18","author":"T Hisamatsu","year":"2019","unstructured":"Hisamatsu T, McGuire M, Wu SY, Rupaimoole R, Pradeep S, Bayraktar E, et al. PRKRA\/PACT expression promotes chemoresistance of mucinous ovarian Cancer. Mol Cancer Ther. 2019;18:162\u201372.","journal-title":"Mol Cancer Ther"},{"key":"2575_CR20","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1038\/s42255-018-0004-9","volume":"1","author":"EJ Hennessy","year":"2019","unstructured":"Hennessy EJ, van Solingen C, Scacalossi KR, Ouimet M, Afonso MS, Prins J, et al. The long noncoding RNA CHROME regulates cholesterol homeostasis in primates. Nat Metab. 2019;1:98\u2013110.","journal-title":"Nat Metab"},{"key":"2575_CR21","doi-asserted-by":"publisher","first-page":"1758","DOI":"10.1038\/ng.3977","volume":"49","author":"DJ Liu","year":"2017","unstructured":"Liu DJ, Peloso GM, Yu H, Butterworth AS, Wang X, Mahajan A, et al. Exome-wide association study of plasma lipids in >\u2009300,000 individuals. Nat Genet. 2017;49:1758\u201366.","journal-title":"Nat Genet"},{"key":"2575_CR22","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s12014-018-9214-0","volume":"15","author":"J Yi","year":"2018","unstructured":"Yi J, Hu H, Shi P, Shi S, Zhao J, Xu L, et al. Differential analysis of quantitative proteome and acetyl-proteome profiling between premenopausal and postmenopausal ovarian tissues. Clin Proteom. 2018;15:36.","journal-title":"Clin Proteom"},{"key":"2575_CR23","doi-asserted-by":"publisher","first-page":"2881","DOI":"10.1210\/en.2013-1385","volume":"155","author":"M Nigro","year":"2014","unstructured":"Nigro M, Santos AT, Barthem CS, Louzada RAN, Fortunato RS, Ketzer LA, et al. A change in liver metabolism but not in brown adipose tissue thermogenesis is an early event in ovariectomy-induced obesity in rats. Endocrinology. 2014;155:2881\u201391.","journal-title":"Endocrinology"},{"key":"2575_CR24","doi-asserted-by":"publisher","first-page":"4527","DOI":"10.3390\/ijms22094527","volume":"22","author":"H Malinsk\u00e1","year":"2021","unstructured":"Malinsk\u00e1 H, H\u00fcttl M, Mikl\u00e1nkov\u00e1 D, Trnovsk\u00e1 J, Zapletalov\u00e1 I, Poruba M, et al. Ovariectomy-Induced hepatic lipid and cytochrome P450 dysmetabolism precedes serum dyslipidemia. Int J Mol Sci. 2021;22:4527.","journal-title":"Int J Mol Sci"},{"key":"2575_CR25","unstructured":"Xu XD, Chen J, Ren J. Experiment of Low-density lipoprotein absorption. Bio-101. 2021;e1010831."},{"key":"2575_CR26","doi-asserted-by":"publisher","first-page":"930","DOI":"10.3389\/fendo.2019.00930","volume":"10","author":"W Fu","year":"2020","unstructured":"Fu W, Gao X-P, Zhang S, Dai Y-P, Zou W-J, Yue L-M. 17\u03b2-Estradiol inhibits PCSK9-Mediated LDLR degradation through GPER\/PLC activation in HepG2 cells. Front Endocrinol (Lausanne). 2020;10:930.","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2575_CR27","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.phymed.2013.07.012","volume":"21","author":"LA Kelly","year":"2014","unstructured":"Kelly LA, Seidlova-Wuttke D, Wuttke W, O\u2019Leary JJ, Norris LA. Estrogen receptor alpha augments changes in hemostatic gene expression in HepG2 cells treated with estradiol and phytoestrogens. Phytomedicine. 2014;21:155\u20138.","journal-title":"Phytomedicine"},{"key":"2575_CR28","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1038\/s41580-019-0190-7","volume":"21","author":"J Luo","year":"2020","unstructured":"Luo J, Yang H, Song B-L. Mechanisms and regulation of cholesterol homeostasis. Nat Rev Mol Cell Biol. 2020;21:225\u201345.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2575_CR29","doi-asserted-by":"publisher","first-page":"2555","DOI":"10.1016\/j.jacc.2018.01.083","volume":"71","author":"D Zhao","year":"2018","unstructured":"Zhao D, Guallar E, Ouyang P, Subramanya V, Vaidya D, Ndumele CE, et al. Endogenous sex hormones and incident cardiovascular disease in Post-Menopausal women. J Am Coll Cardiol. 2018;71:2555\u201366.","journal-title":"J Am Coll Cardiol"},{"key":"2575_CR30","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/S2213-8587(22)00076-6","volume":"10","author":"RE Nappi","year":"2022","unstructured":"Nappi RE, Chedraui P, Lambrinoudaki I, Simoncini T. Menopause: a cardiometabolic transition. Lancet Diabetes Endocrinol. 2022;10:442\u201356.","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2575_CR31","doi-asserted-by":"publisher","first-page":"3841","DOI":"10.1038\/s41598-021-82837-6","volume":"11","author":"VT Boldarine","year":"2021","unstructured":"Boldarine VT, Joyce E, Pedroso AP, Telles MM, Oyama LM, Bueno AA, et al. Oestrogen replacement fails to fully revert ovariectomy-induced changes in adipose tissue monoglycerides, diglycerides and cholesteryl esters of rats fed a lard-enriched diet. Sci Rep. 2021;11:3841.","journal-title":"Sci Rep"},{"key":"2575_CR32","doi-asserted-by":"publisher","first-page":"k4810","DOI":"10.1136\/bmj.k4810","volume":"364","author":"Y Vinogradova","year":"2019","unstructured":"Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ. 2019;364:k4810.","journal-title":"BMJ"},{"key":"2575_CR33","doi-asserted-by":"publisher","first-page":"n2182","DOI":"10.1136\/bmj.n2182","volume":"374","author":"Y Vinogradova","year":"2021","unstructured":"Vinogradova Y, Dening T, Hippisley-Cox J, Taylor L, Moore M, Coupland C. Use of menopausal hormone therapy and risk of dementia: nested case-control studies using QResearch and CPRD databases. BMJ. 2021;374:n2182.","journal-title":"BMJ"},{"key":"2575_CR34","doi-asserted-by":"publisher","first-page":"m3873","DOI":"10.1136\/bmj.m3873","volume":"371","author":"Y Vinogradova","year":"2020","unstructured":"Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases. BMJ. 2020;371:m3873.","journal-title":"BMJ"},{"key":"2575_CR35","doi-asserted-by":"publisher","first-page":"E908","DOI":"10.1152\/ajpendo.00466.2018","volume":"316","author":"J Buniam","year":"2019","unstructured":"Buniam J, Chukijrungroat N, Khamphaya T, Weerachayaphorn J, Saengsirisuwan V. Estrogen and voluntary exercise attenuate cardiometabolic syndrome and hepatic steatosis in ovariectomized rats fed a high-fat high-fructose diet. Am J Physiol Endocrinol Metab. 2019;316:E908\u201321.","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2575_CR36","doi-asserted-by":"publisher","first-page":"17093","DOI":"10.1038\/nrdp.2017.93","volume":"3","author":"JC Defesche","year":"2017","unstructured":"Defesche JC, Gidding SS, Harada-Shiba M, Hegele RA, Santos RD, Wierzbicki AS. Familial hypercholesterolaemia. Nat Rev Dis Primers. 2017;3:17093.","journal-title":"Nat Rev Dis Primers"},{"key":"2575_CR37","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1210\/endrev\/bnab035","volume":"43","author":"NG Seidah","year":"2022","unstructured":"Seidah NG, Prat A. The multifaceted biology of PCSK9. Endocr Rev. 2022;43:558\u201382.","journal-title":"Endocr Rev"},{"key":"2575_CR38","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1038\/nrendo.2016.164","volume":"13","author":"RA Lobo","year":"2017","unstructured":"Lobo RA. Hormone-replacement therapy: current thinking. Nat Rev Endocrinol. 2017;13:220\u201331.","journal-title":"Nat Rev Endocrinol"},{"key":"2575_CR39","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1210\/endrev\/bnab011","volume":"42","author":"VA Flores","year":"2021","unstructured":"Flores VA, Pal L, Manson JE. Hormone therapy in menopause: concepts, controversies, and approach to treatment. Endocr Rev. 2021;42:720\u201352.","journal-title":"Endocr Rev"}],"container-title":["Lipids in Health and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12944-025-02575-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12944-025-02575-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12944-025-02575-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,10]],"date-time":"2025-05-10T19:02:11Z","timestamp":1746903731000},"score":1,"resource":{"primary":{"URL":"https:\/\/lipidworld.biomedcentral.com\/articles\/10.1186\/s12944-025-02575-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,10]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2575"],"URL":"https:\/\/doi.org\/10.1186\/s12944-025-02575-w","relation":{},"ISSN":["1476-511X"],"issn-type":[{"value":"1476-511X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,10]]},"assertion":[{"value":"5 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal procedures performed in this study adhered strictly to both international and local ethical standards for animal research and have received approval from the Animal Welfare and Ethics Group, Department of Laboratory Animal Science, Fudan University (Approval ID: 202311011Z).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"This manuscript has received unanimous approval from all the authors for publication.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"171"}}