Sterol regulatory element-binding protein 1c (SREBP-1c) (SREBP-1c)

Sterol regulatory element-binding protein 1c (SREBP-1c) is a critical transcription factor that serves as a master regulator of fatty acid synthesis and lipid storage in the liver. It is primarily activated by insulin signaling and high glucose levels, leading to the transcriptional upregulation of key downstream lipogenic enzymes including Acetyl-CoA Carboxylase (ACC), Fatty Acid Synthase (FASN), and Stearoyl-CoA Desaturase-1 (SCD1) (UniProt P36956; PMID: 29438336). In metabolic diseases such as MASLD and type 2 diabetes, the SREBP-1c pathway is often overactive, driving excessive hepatic de novo lipogenesis and contributing to steatosis and insulin resistance (PMID: 30107159). Therapeutic strategies targeting this pathway include small molecules that inhibit SREBP-1c processing or direct inhibitors of its downstream enzymatic effectors like ACC and FASN. While effective at reducing liver fat, targeting this pathway requires careful management of systemic lipid profiles, as some inhibitors have been linked to elevations in circulating triglycerides (PMID: 32454456).

Other names

Sterol regulatory element-binding transcription factor 1SREBF1Adipocyte determination- and differentiation-dependent factor 1ADD1SREBP1c

Inhibition of SREBP-1c activation by preventing its translocation from the endoplasmic reticulum to the Golgi apparatus, or direct inhibition of downstream enzymes such as Acetyl-CoA Carboxylase (ACC) and Fatty Acid Synthase (FASN) to suppress the synthesis of long-chain fatty acids.