出版社：American Society for Biochemistry and Molecular Biology
摘要：Sterol regulatory element-binding protein (SREBP)-1c is nowwell established as a key transcription factor for the regulationof lipogenic enzyme genes such as FAS in hepatocytes. Meanwhile,the mechanisms of lipogenic gene regulation in adipocytes remainunclear. Here, we demonstrate that those in adipocytes are independentof SREBP-1c. In adipocytes, unlike in hepatocytes, the stimulationof SREBP-1c expression by liver X receptor agonist does notaccompany lipogenic gene upregulation, although nuclear SREBP-1cprotein is concomitantly increased, indicating that the activationprocess of SREBP-1c by the cleavage system is intact in adipocytes.Supportively, transcriptional activity of the mature form ofSREBP-1c for the FAS promoter was negligible when measured byreporter analysis. As an underlying mechanism, accessibilityof SREBP-1c to the functional elements was involved, becausechromatin immunoprecipitation assays revealed that SREBP-1cdoes not bind to the functional SRE/E-box site on the FAS promoterin adipocytes. Moreover, genetic disruption of SREBP-1 did notcause any changes in lipogenic gene expression in adipose tissue.In summary, in adipocytes, unlike in hepatocytes, incrementsin nuclear SREBP-1c are not accompanied by transactivation oflipogenic genes; thus, SREBP-1c is not committed to the regulationof lipogenesis.Supplementary key words sterol regulatory element-binding protein • lipogenesis • fatty acid synthase
Abbreviations: ACC, acetyl-coenzyme A carboxylase; ALLN, N-acetyl-leucyl-leucyl-norleucinal; ChIP, chromatin immunoprecipitation; LXR, liver X receptor; RXR, retinoid X receptor; SREBP, sterol regulatory element-binding protein
