{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chang M"],"funding":["National Institute of Diabetes and Digestive and Kidney Diseases","NIDDK NIH HHS","University of California, San Francisco","National Institutes of Health"],"pagination":["110353"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12274751"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["301(7)"],"pubmed_abstract":["Glucocorticoids are potent anti-inflammatory agents that are frequently used to treat inflammatory and autoimmune diseases. Chronic glucocorticoid treatment, however, causes unwanted adverse effects such as hypertriglyceridemia and hepatic steatosis. Here we showed that reducing the expression of sphingosine-1-phosphate receptor 2 (S1PR2) in mice liver reduced chronic glucocorticoid exposure induced triglyceride accumulation in the liver and the plasma. Chronic glucocorticoid treatment increased the recruitment of sterol regulatory element-binding protein 1c (Srebp1c) to the sterol regulatory element of mouse fatty acid synthase (Fasn) gene. This response was attenuated in hepatic S1PR2 knockdown mice. Chronic glucocorticoid treatment also increased the recruitment of carbohydrate response element binding protein (ChREBP) to the carbohydrate response elements (ChoREs) of lipogenic and glycolytic genes. This response was partially reduced in hepatic S1PR2 knockdown mice. Reducing hepatic ChREBP expression reduced the expression of Pklr, Me1, and Fasn. However, long-term glucocorticoid induced triglyceride accumulation in the liver and the plasma were not affected whereas the hepatic lactate levels were decreased. Thus, ChREBP plays a major role in chronic glucocorticoid induced glycolysis whereas its role in hypertriglyceridemia and hepatic steatosis was modest. Overall, this study demonstrated that hepatic S1PR2 signaling plays a partial but significant role in chronic glucocorticoid exposure-activated Srebp1c and ChREBP which promote lipogenesis and glycolysis, respectively."],"journal":["The Journal of biological chemistry"],"pubmed_title":["The sphingosine-1-phosphate receptor 2 S1PR2 mediates chronic glucocorticoid exposure-induced hepatic steatosis and hypertriglyceridemia."],"pmcid":["PMC12274751"],"funding_grant_id":["P30 DK026743","DK131194","DK124866","R01 DK113019"],"pubmed_authors":["Chang M","Zhao M","Scott DK","Wang JC","Lee RA","Whang EM"],"additional_accession":[]},"is_claimable":false,"name":"The sphingosine-1-phosphate receptor 2 S1PR2 mediates chronic glucocorticoid exposure-induced hepatic steatosis and hypertriglyceridemia.","description":"Glucocorticoids are potent anti-inflammatory agents that are frequently used to treat inflammatory and autoimmune diseases. Chronic glucocorticoid treatment, however, causes unwanted adverse effects such as hypertriglyceridemia and hepatic steatosis. Here we showed that reducing the expression of sphingosine-1-phosphate receptor 2 (S1PR2) in mice liver reduced chronic glucocorticoid exposure induced triglyceride accumulation in the liver and the plasma. Chronic glucocorticoid treatment increased the recruitment of sterol regulatory element-binding protein 1c (Srebp1c) to the sterol regulatory element of mouse fatty acid synthase (Fasn) gene. This response was attenuated in hepatic S1PR2 knockdown mice. Chronic glucocorticoid treatment also increased the recruitment of carbohydrate response element binding protein (ChREBP) to the carbohydrate response elements (ChoREs) of lipogenic and glycolytic genes. This response was partially reduced in hepatic S1PR2 knockdown mice. Reducing hepatic ChREBP expression reduced the expression of Pklr, Me1, and Fasn. However, long-term glucocorticoid induced triglyceride accumulation in the liver and the plasma were not affected whereas the hepatic lactate levels were decreased. Thus, ChREBP plays a major role in chronic glucocorticoid induced glycolysis whereas its role in hypertriglyceridemia and hepatic steatosis was modest. Overall, this study demonstrated that hepatic S1PR2 signaling plays a partial but significant role in chronic glucocorticoid exposure-activated Srebp1c and ChREBP which promote lipogenesis and glycolysis, respectively.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jun","modification":"2025-08-27T03:06:46.927Z","creation":"2025-08-27T03:06:46.927Z"},"accession":"S-EPMC12274751","cross_references":{"pubmed":["40490140"],"doi":["10.1016/j.jbc.2025.110353"]}}