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The current study explored the mechanisms involved in hypertriglyceridaemia during pregnancy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Lipid profile and expression levels of key genes involved in liver TG metabolism in non\u2010pregnant and pregnant mice were studied. The effects of pregnancy\u2010related hormones on key genes and the underlying mechanisms were uncovered in vitro and in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Plasma and hepatic TG levels were elevated, while hepatic fatty acid translocase (FAT\/CD36) was up\u2010regulated in pregnant mice. Corticosterone and cortisol (endogenous glucocorticoids that are elevated during pregnancy), but not oestradiol or progesterone, significantly up\u2010regulated CD36 in hepatocytes, and this was abolished after knockdown of the glucocorticoid receptor (GR) using a siRNA or in the presence of GR antagonists, RU486 and AL082D06. The luciferase reporter gene and chromatin immunoprecipitation assay further revealed that corticosterone\/cortisol promoted the direct binding of GR to the CD36 promoter and up\u2010regulated its transcription. Chronic corticosterone exposure induced liver lipid accumulation and increased plasma TG levels in mice, which were attenuated by RU486 via inhibition of the GR\u2010CD36 pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Increased corticosterone\/cortisol induces liver lipid accumulation and hypertriglyceridaemia during pregnancy by accelerating fatty acid uptake into hepatocytes via activation of GR and its target gene, CD36. Our results may be useful for the prevention of severe hypertriglyceridaemia and associated pregnancy complications.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15863","type":"journal-article","created":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T01:56:56Z","timestamp":1651456616000},"page":"4440-4456","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Up\u2010regulation of hepatic CD36 by increased corticosterone\/cortisol levels via GR leads to lipid accumulation in liver and hypertriglyceridaemia during pregnancy"],"prefix":"10.1111","volume":"179","author":[{"given":"Mengru","family":"Bai","sequence":"first","affiliation":[{"name":"Laboratory of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences Zhejiang University  Hangzhou China"},{"name":"Department of Clinical Pharmacy, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated 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