{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Tiwari V"],"funding":["Alfred E. Mann Family Foundation Arthur Riggs Diabetes and Metabolism Research Institute","NIDDK NIH HHS","Burroughs Wellcome Fund","NHLBI NIH HHS","NCI NIH HHS","American Diabetes Association","U.S. Department of Health & Human Services | National Institutes of Health (NIH)","American Diabetes Association (ADA)","U.S. Department of Health & Human Services | National Institutes of Health"],"pagination":["2284-2299"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12638245"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7(11)"],"pubmed_abstract":["Citrin deficiency (CD) is caused by the inactivation of SLC25A13, a mitochondrial membrane protein required to move electrons from cytosolic NADH to the mitochondrial matrix in hepatocytes. People with CD do not like sweets. Here we show that SLC25A13 loss causes the accumulation of glycerol-3-phosphate (G3P), which activates the carbohydrate response element-binding protein (ChREBP) to transcribe FGF21, which acts in the brain to restrain intake of sweets and alcohol and to transcribe key genes driving lipogenesis. Mouse and human data suggest that G3P-ChREBP is a mechanistic component of the Randle Cycle that contributes to metabolic-dysfunction-associated steatotic liver disease and forms part of a system that communicates metabolic states from the liver to the brain in a manner that al"],"journal":["Nature metabolism"],"pubmed_title":["Glycerol-3-phosphate activates ChREBP, FGF21 transcription and lipogenesis in citrin deficiency."],"pmcid":["PMC12638245"],"funding_grant_id":["11-22-JDFPM-06","P30CA33572","R01DK012170","P30 CA033572","R01 HL147545","R01HL147545","R01 DK100425","R01 DK134675","R01DK134675","R01DK100425","R01 DK136671","R01 DK118011","R01DK136671","R01DK118011"],"pubmed_authors":["Tiwari V","Sun O","Goodman RP","Jin B","Lopez Gonzalez EDJ","Chen MH","Brenner C","Herman MA","Shah H","Zhang A","Wu X","Spracklen CN"],"additional_accession":[]},"is_claimable":false,"name":"Glycerol-3-phosphate activates ChREBP, FGF21 transcription and lipogenesis in citrin deficiency.","description":"Citrin deficiency (CD) is caused by the inactivation of SLC25A13, a mitochondrial membrane protein required to move electrons from cytosolic NADH to the mitochondrial matrix in hepatocytes. People with CD do not like sweets. Here we show that SLC25A13 loss causes the accumulation of glycerol-3-phosphate (G3P), which activates the carbohydrate response element-binding protein (ChREBP) to transcribe FGF21, which acts in the brain to restrain intake of sweets and alcohol and to transcribe key genes driving lipogenesis. Mouse and human data suggest that G3P-ChREBP is a mechanistic component of the Randle Cycle that contributes to metabolic-dysfunction-associated steatotic liver disease and forms part of a system that communicates metabolic states from the liver to the brain in a manner that al","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-06-05T17:08:18.013Z","creation":"2026-05-19T03:11:35.581Z"},"accession":"S-EPMC12638245","cross_references":{"pubmed":["41238906"],"doi":["10.1038/s42255-025-01399-3"]}}