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PE has long been characterized by deficient trophoblast invasion into the uterus and consequent placental hypoperfusion, yet the upstream causative factors and effective interventional targets for PE remain unknown. Alterations in the metabolism of preeclamptic placentas are thought to result from placental ischemia, while disturbances of the metabolism and of metabolites in PE pathogenesis are largely ignored. In fact, as one of the largest fetal organs at birth, the placenta consumes a considerable amount of glucose and fatty acid. Increasing evidence suggests glucose and fatty acid exist as energy substrates and regulate placental development through bioactive derivates. Moreover, recent findings have revealed that the placental metabolism adapts readily to environmental changes, altering its response to nutrients and endocrine signals; this adaptability optimizes pregnancy outcomes by diversifying available carbon sources for energy production, hormone synthesis, angiogenesis, immune activation, and tolerance, and fetoplacental growth. These observations raise the possibility that carbohydrate and lipid metabolism abnormalities play a role in both the etiology and clinical progression of PE, sparking a renewed interest in the interrelationship between PE and metabolic dysregulation. This review will focus on key metabolic substrates and regulatory molecules in the placenta and aim to provide novel insights with respect to the metabolism\u2019s role in modulating placental development and functions. Further investigations from this perspective are poised to decipher the etiology of PE and suggest potential therapies.<\/jats:p>","DOI":"10.1111\/febs.15745","type":"journal-article","created":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T12:28:51Z","timestamp":1612528131000},"page":"336-354","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":77,"title":["Revisiting preeclampsia: a metabolic disorder of the placenta"],"prefix":"10.1111","volume":"289","author":[{"given":"Mingyu","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Obstetrics The First Affiliated Hospital of Chongqing Medical University China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0899-4412","authenticated-orcid":false,"given":"Ji","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Surgery Morsani College of Medicine University of South Florida Tampa FL 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