Sterol regulatory element-binding transcription factor 1 (SREBF1) (SREBF1)

Sterol regulatory element-binding transcription factor 1 (SREBF1) is a critical gene encoding the SREBP-1 protein, a master regulator of lipid and cholesterol metabolism (UniProt P36956). It exists in two main isoforms, SREBP-1a and SREBP-1c, with SREBP-1c being the primary isoform in the liver that mediates insulin-induced de novo lipogenesis (NCBI Gene 6720). SREBP-1 activates the transcription of key enzymes such as fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC), making it a central player in hepatic lipid accumulation. Dysregulation of SREBF1 is strongly linked to metabolic disorders, including non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (PubMed PMID: 28844017). Therapeutic targeting of SREBF1 mRNA using antisense oligonucleotides (ASOs) or siRNA aims to reduce SREBP-1 protein levels and alleviate steatosis. While small molecules like fatostatin inhibit the protein's activation, mRNA-targeted therapies offer high specificity for treating metabolic syndrome and potentially certain cancers (PubMed PMID: 19111664).

Other names

SREBP1SREBP-1ADD1BHLHD1Sterol regulatory element-binding protein 1Adipocyte determination- and differentiation-dependent factor 1

Antisense oligonucleotides (ASOs) or siRNA target SREBF1 mRNA to induce its degradation via RNase H or the RNA-induced silencing complex (RISC), respectively, thereby preventing the translation of SREBP-1 protein and reducing the expression of downstream lipogenic genes.