{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Lee HK"],"funding":["NIDDK NIH HHS"],"pubmed_abstract":["Growth hormone (GH) signaling through STAT5B is a central regulator of hepatic metabolism, yet the functional consequences of disease-associated STAT5B variants remain poorly understood. Here, we analyzed mice carrying STAT5B<sup>Y665F</sup> (gain-of-function) and STAT5B<sup>Y665H</sup> (loss-of-function) variants and dissect their impact on metabolic regulation. STAT5B<sup>Y665F</sup> mice developed hepatic lipid accumulation, hypercholesterolemia, and enhanced insulin sensitivity, whereas STAT5B<sup>Y665H</sup> mice displayed reduced body weight and impaired insulin responsiveness. Transcriptomic analyses revealed that STAT5B<sup>Y665F</sup> activated lipid, cholesterol, and immune transcriptional programs, while STAT5B<sup>Y665H</sup> failed to induce these pathways. Notably, STAT5B<sup"],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2025.11.27.691004"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12694592"],"repository":["biostudies-literature"],"pubmed_title":["Disease-associated mutations in the STAT5B SH2 domain reprogram hepatic cholesterol and lipid metabolism."],"pmcid":["PMC12694592"],"funding_grant_id":["R01 DK121998"],"pubmed_authors":["Hennighausen L","Waxman DJ","Pyatkov M","Liu N","Ye B","Demby T","Lee HK","Furth PA","Gavrilova O"],"additional_accession":[]},"is_claimable":false,"name":"Disease-associated mutations in the STAT5B SH2 domain reprogram hepatic cholesterol and lipid metabolism.","description":"Growth hormone (GH) signaling through STAT5B is a central regulator of hepatic metabolism, yet the functional consequences of disease-associated STAT5B variants remain poorly understood. Here, we analyzed mice carrying STAT5B<sup>Y665F</sup> (gain-of-function) and STAT5B<sup>Y665H</sup> (loss-of-function) variants and dissect their impact on metabolic regulation. STAT5B<sup>Y665F</sup> mice developed hepatic lipid accumulation, hypercholesterolemia, and enhanced insulin sensitivity, whereas STAT5B<sup>Y665H</sup> mice displayed reduced body weight and impaired insulin responsiveness. Transcriptomic analyses revealed that STAT5B<sup>Y665F</sup> activated lipid, cholesterol, and immune transcriptional programs, while STAT5B<sup>Y665H</sup> failed to induce these pathways. Notably, STAT5B<sup","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Dec","modification":"2026-06-04T03:20:58.73Z","creation":"2026-06-04T03:12:38.467Z"},"accession":"S-EPMC12694592","cross_references":{"pubmed":["41383779"],"doi":["10.1101/2025.11.27.691004"]}}