{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:44:39Z","timestamp":1791999879303,"version":"4.4.0"},"reference-count":56,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T00:00:00Z","timestamp":1652745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["P20GM135002 (JLS)"],"award-info":[{"award-number":["P20GM135002 (JLS)"]}]},{"name":"National Institutes of Health","award":["5R01DK124806"],"award-info":[{"award-number":["5R01DK124806"]}]},{"name":"National Institutes of Health","award":["5R01NR017644"],"award-info":[{"award-number":["5R01NR017644"]}]},{"name":"National Institutes of Health","award":["P30DK072476"],"award-info":[{"award-number":["P30DK072476"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Preeclampsia (PE), an inflammatory state during pregnancy, is a significant cause of maternal and fetal morbidity and mortality. Adverse outcomes associated with PE include hypertension, proteinuria, uterine\/placental abnormalities, fetal growth restriction, and pre-term birth. Women with obesity have an increased risk of developing PE likely due to impaired placental development from altered metabolic homeostasis. Inflammatory cytokines from maternal adipose tissue and circulating cholesterol have been linked to systemic inflammation, hypertension, and other adverse outcomes associated with PE. This review will summarize the current knowledge on the role of nutrients, obesity, and cholesterol signaling in PE with an emphasis on findings from preclinical models.<\/jats:p>","DOI":"10.3390\/nu14102087","type":"journal-article","created":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T04:04:19Z","timestamp":1652760259000},"page":"2087","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["An Overview of Obesity, Cholesterol, and Systemic Inflammation in Preeclampsia"],"prefix":"10.3390","volume":"14","author":[{"given":"Morgan C.","family":"Alston","sequence":"first","affiliation":[{"name":"Departments of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA"},{"name":"Reproductive Endocrinology and Women\u2019s Health Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7267-7374","authenticated-orcid":false,"given":"Leanne M.","family":"Redman","sequence":"additional","affiliation":[{"name":"Reproductive Endocrinology and Women\u2019s Health Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5360-1243","authenticated-orcid":false,"given":"Jennifer L.","family":"Sones","sequence":"additional","affiliation":[{"name":"Departments of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA"},{"name":"Reproductive Endocrinology and Women\u2019s Health Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1042\/CS20160832","article-title":"Visceral adipose tissue activated macrophage content and inflammatory adipokine secretion is higher in pre-eclampsia than in healthy pregnancys","volume":"131","author":"Huda","year":"2017","journal-title":"Clin. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1161\/CIRCRESAHA.118.313276","article-title":"Preeclampsia: Pathophysiology, challenges, and perspectives","volume":"124","author":"Rana","year":"2019","journal-title":"Circ. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2632637","DOI":"10.1155\/2018\/2632637","article-title":"Clinical presentation of preeclampsia and the diagnostic value of proteins and their methylation products as biomarkers in pregnant women with preeclampsia and their newborns","volume":"2018","author":"Portelli","year":"2018","journal-title":"J. Pregnancy"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/1477-7827-7-70","article-title":"Potential markers of preeclampsia\u2013a review","volume":"7","author":"Grill","year":"2009","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1159\/000477903","article-title":"Update on the Diagnosis and Prognosis of Preeclampsia with the Aid of the SFlt-1\/ PlGF Ratio in Singleton Pregnancies","volume":"43","author":"Herraiz","year":"2018","journal-title":"Fetal Diagn. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1093\/advances\/nmy055","article-title":"Humans against Obesity: Who Will Win?","volume":"10","author":"Caballero","year":"2019","journal-title":"Adv. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1161\/ATVBAHA.107.157685","article-title":"Dietary Cholesterol worsens adipose tissue macrophage accumulation and atherosclerosis in obese LDL receptor\u2013deficient mice","volume":"28","author":"Subramanian","year":"2008","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"R485","DOI":"10.1152\/ajpregu.00512.2016","article-title":"Adverse metabolic phenotype of female offspring exposed to preeclampsia in utero: A characterization of the BPH\/5 mouse in postnatal life","volume":"312","author":"Sutton","year":"2017","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"325932","DOI":"10.1155\/2015\/325932","article-title":"Involvement of Visceral Adipose Tissue in Immunological Modulation of Inflammatory Cascade in Preeclampsia","volume":"2015","author":"Naruse","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1530\/REP-10-0074","article-title":"Obesity, pregnancy, inflammation, and vascular function","volume":"140","author":"Denison","year":"2010","journal-title":"Reproduction"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"a023010","DOI":"10.1101\/cshperspect.a023010","article-title":"Molecular Cross-Talk at the Feto-Maternal Interface","volume":"5","author":"Lash","year":"2015","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3142","DOI":"10.3390\/biom5043142","article-title":"Immune Mechanisms Linking Obesity and Preeclampsia","volume":"5","author":"Spradley","year":"2015","journal-title":"Biomolecules"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"R5","DOI":"10.1152\/ajpregu.00440.2016","article-title":"Metabolic abnormalities and obesity\u2019s impact on the risk for developing preeclampsia","volume":"312","author":"Spradley","year":"2017","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.metabol.2014.09.010","article-title":"Structure, production and signaling of leptin","volume":"64","author":"Morrison","year":"2015","journal-title":"Metabolism"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1111\/jcmm.13369","article-title":"Leptin action in normal and pathological pregnancies","volume":"22","author":"Toro","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.cyto.2016.10.011","article-title":"leptin in inflammation and autoimmunity","volume":"98","year":"2017","journal-title":"Cytokine"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"184","DOI":"10.4254\/wjh.v4.i6.184","article-title":"Regulation and deregulation of cholesterol homeostasis: The liver as a metabolic \u201cpower station\u201d","volume":"4","author":"Trapani","year":"2012","journal-title":"World J. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1097\/MOL.0000000000000260","article-title":"Dietary cholesterol effects on adipose tissue inflammation","volume":"27","author":"Chung","year":"2016","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_19","unstructured":"Craig, M., Yarrarapu, S.N.S., and Dimri, M. (2022). Biochemistry, Cholesterol. StatPearls, StatPearls Publishing."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nri3793","article-title":"Cholesterol, Inflammation and Innate Immunity","volume":"15","author":"Tall","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.placenta.2021.02.019","article-title":"Effects of lipoproteins on endothelial cells and macrophages function and its possible implications on fetal adverse outcomes associated to maternal hypercholesterolemia during pregnancy","volume":"106","author":"Cantin","year":"2021","journal-title":"Placenta"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.placenta.2020.03.007","article-title":"Maternal hypercholesterolemia during pregnancy: Potential modulation of cholesterol transport through the human placenta and lipoprotein profile in maternal and neonatal circulation","volume":"94","author":"Cantin","year":"2020","journal-title":"Placenta"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.mehy.2004.04.026","article-title":"The role of lipoprotein (a) in pregnancies complicated by pre-eclampsia","volume":"64","author":"Manten","year":"2005","journal-title":"Med. Hypotheses"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s12944-018-0698-4","article-title":"Lipoprotein turnover and possible remnant accumulation in preeclampsia: Insights from the Freiburg Preeclampsia H.E.L.P.-Apheresis Study","volume":"17","author":"Contini","year":"2018","journal-title":"Lipids Health Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1093\/aje\/kwu145","article-title":"Maternal Hyperlipidemia and the Risk of Preeclampsia: A Meta-Analysis","volume":"180","author":"Spracklen","year":"2014","journal-title":"Am. J. Epidemiol."},{"key":"ref_26","first-page":"848","article-title":"Administration of natural anthocyanins derived from chokeberry retardation of idiopathic and preeclamptic origin. Influence on metabolism of plasma oxidized lipoproteins: The role of autoantibodies to oxidized low density lipoproteins","volume":"71","author":"Stachowiak","year":"2000","journal-title":"Ginekol. Pol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0301-2115(01)00384-0","article-title":"The effect of garlic tablet on plasma lipids and platelet aggregation in nulliparous pregnants at high risk of preeclampsia","volume":"99","author":"Ziaei","year":"2001","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/S0895-7061(03)00897-5","article-title":"Plasma Carotenoids, Retinol, Tocopherols, and Lipoproteins in Preeclamptic and Normotensive Pregnant Zimbabwean Women","volume":"16","author":"Williams","year":"2003","journal-title":"Am. J. Hypertens."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.stemcr.2018.07.004","article-title":"Self-Renewing Trophoblast Organoids Recapitulate the Developmental Program of the Early Human Placenta","volume":"1","author":"Haider","year":"2018","journal-title":"Stem Cell Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"R49","DOI":"10.1152\/ajpregu.00334.2018","article-title":"Dyslipidemia and the role of adipose tissue in early pregnancy in the bph\/5 mouse model for preeclampsia","volume":"317","author":"Reijnders","year":"2019","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1161\/01.HYP.35.1.367","article-title":"Decreased Endothelium-Dependent Vascular Relaxation during Reduction of Uterine Perfusion Pressure in Pregnant Rat","volume":"35","author":"Crews","year":"2000","journal-title":"Hypertension"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Johnson, A.C., Tremble, S.M., Chan, S.-L., Moseley, J., LaMarca, B., Nagle, K.J., and Cipolla, M.J. (2014). Magnesium Sulfate Treatment Reverses Seizure Susceptibility and Decreases Neuroinflammation in a Rat Model of Severe Preeclampsia. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0113670"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1177\/1933719112459228","article-title":"Pregnancy Enhances the Effects of Hypercholesterolemia on Posterior Cerebral Arteries","volume":"20","author":"Schreurs","year":"2013","journal-title":"Reprod. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e08491","DOI":"10.1016\/j.heliyon.2021.e08491","article-title":"Hyperleptinemia results in systemic inflammation and the exacerbation of ischemia-reperfusion myocardial injury","volume":"7","author":"Polyakova","year":"2021","journal-title":"Heliyon"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1042\/CS20200764","article-title":"High-Cholesterol Diet during Pregnancy Induces Maternal Vascular Dysfunction in Mice: Potential Role for Oxidized LDL-Induced LOX-1 and AT1 Receptor Activation","volume":"134","author":"Spaans","year":"2020","journal-title":"Clin. Sci. (Lond.)"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s10557-011-6335-3","article-title":"LOX-1 and Obesity","volume":"25","author":"Yan","year":"2011","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.placenta.2009.07.012","article-title":"Effect of Heme Oxygenase-1 Deficiency on Placental Development","volume":"30","author":"Zhao","year":"2009","journal-title":"Placenta"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"(2018). ACOG Committee Opinion No. 743: Low-Dose Aspirin Use During Pregnancy. Obstet. Gynecol., 132, e44\u2013e52.","DOI":"10.1097\/AOG.0000000000002708"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.placenta.2015.01.004","article-title":"Aspirin inhibits expression of sflt1 from human cytotrophoblasts induced by hypoxia, via cyclo-oxygenase 1","volume":"36","author":"Li","year":"2015","journal-title":"Placenta"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"100003","DOI":"10.1016\/j.xagr.2021.100003","article-title":"Safety of daily low-dose aspirin use during pregnancy in low-income and middle-income countries","volume":"1","author":"Short","year":"2021","journal-title":"AJOG Glob. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e22801","DOI":"10.1097\/MD.0000000000022801","article-title":"Efficacy and Safety of Low Dose Aspirin and Magnesium Sulfate in the Treatment of Pregnancy Induced Hypertension: A Protocol for Systematic Review and Meta-Analysis","volume":"99","author":"He","year":"2020","journal-title":"Medicine"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"S1108","DOI":"10.1016\/j.ajog.2020.08.045","article-title":"Prevention of preeclampsia with aspirin","volume":"226","author":"Rolnik","year":"2022","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1152\/physiolgenomics.00115.2017","article-title":"Celecoxib Restores Angiogenic Factor Expression at the Maternal-Fetal Interface in the BPH\/5 Mouse Model of Preeclampsia","volume":"50","author":"Reijnders","year":"2018","journal-title":"Physiol. Genom."},{"key":"ref_44","first-page":"1371","article-title":"NSAID Prescribing Precautions","volume":"80","author":"Risser","year":"2009","journal-title":"Am. Fam. Physician"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.tjog.2022.02.015","article-title":"The Effect of celecoxib for treatment of preterm labor on fetuses during the second trimester of pregnancy: A Pilot Case Series","volume":"61","author":"Ohtsuki","year":"2022","journal-title":"Taiwan J. Obstet. Gynecol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s11906-020-1026-8","article-title":"Novel Interventions for the Prevention of Preeclampsia","volume":"22","author":"Rood","year":"2020","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1080\/13543784.2016.1196185","article-title":"The early developments of preeclampsia drugs","volume":"25","author":"Costantine","year":"2016","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e118","DOI":"10.1161\/HYPERTENSIONAHA.114.03115","article-title":"Clinical Improvement and Successful Pregnancy in a Preeclamptic Patient with Antiphospholipid Syndrome Treated with Pravastatin","volume":"63","author":"Lefkou","year":"2014","journal-title":"Hypertension"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/j.jacl.2016.07.002","article-title":"The Risks of Statin Use in Pregnancy: A Systematic Review","volume":"10","author":"Karalis","year":"2016","journal-title":"J. Clin. Lipidol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.bbrc.2019.10.186","article-title":"Tadalafil alleviates preeclampsia and fetal growth restriction in RUPP model of preeclampsia in mice","volume":"521","author":"Sekimoto","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1080\/14767058.2018.1438401","article-title":"Cardiac function and tadalafil used for treating fetal growth restriction in pregnant women without cardiovascular disease","volume":"32","author":"Tanaka","year":"2019","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1111\/jog.13345","article-title":"Safety and Dose-Finding Trial of Tadalafil Administered for Fetal Growth Restriction: A Phase-1 Clinical Study","volume":"43","author":"Kubo","year":"2017","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1111\/j.1471-0528.2012.03430.x","article-title":"Sildenafil citrate improves perinatal outcome in fetuses from pre-eclamptic rats","volume":"119","author":"Herraiz","year":"2012","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1159\/000453062","article-title":"Sildenafil in Pregnancy: A Systematic Review of Maternal Tolerance and Obstetric and Perinatal Outcomes","volume":"41","author":"Dunn","year":"2017","journal-title":"Fetal Diagn. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4604","DOI":"10.1074\/jbc.M114.605642","article-title":"Enriched Environment-Induced Maternal Weight Loss Reprograms Metabolic Gene Expression in Mouse Offspring","volume":"290","author":"Wei","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1471-0528.2010.02761.x","article-title":"Associations of gestational weight loss with birth-related outcome: A retrospective cohort study","volume":"118","author":"Beyerlein","year":"2011","journal-title":"BJOG Int. J. Obstet. 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