Transcriptional suppression of human microsomal triglyceride transfer protein by hypolipidemic insulin sensitizers.

Microsomal triglyceride transfer protein (MTP) catalyzes the assembly and secretion of liver triglyceride-rich lipoproteins. The human MTP (hMTP) promoter activity is reported here to be suppressed by HNF-4alpha ligand antagonists (e.g.

Thioesterase activity and acyl-CoA/fatty acid cross-talk of hepatocyte nuclear factor-4{alpha}.

Hepatocyte nuclear factor-4alpha (HNF-4alpha) activity is modulated by natural and xenobiotic fatty acid and fatty acyl-CoA ligands as a function of their chain length, unsaturation, and substitutions. The acyl-CoA site of HNF-4alpha is reported here to consist of the E-F domain, to bind long-chain acyl-CoAs but not the respective free acids, and to catalyze the hydrolysis of bound fatty acyl-CoAs. The free acid pocket, previously reported in the x-ray structure of HNF-4alpha E-domain, entraps fatty acids but excludes acyl-CoAs.

Negative autoregulation of HNF-4alpha gene expression by HNF-4alpha1.

HNF-4alpha (hepatocyte nuclear factor-4alpha) is required for tissue-specific expression of many of the hepatic, pancreatic, enteric and renal traits. Heterozygous HNF-4alpha mutants are inflicted by MODY-1 (maturity onset diabetes of the young type-1). HNF-4alpha expression is reported here to be negatively autoregulated by HNF-4alpha1 and to be activated by dominant-negative HNF-4alpha1.

Transcriptional regulation of human microsomal triglyceride transfer protein by hepatocyte nuclear factor-4alpha.

Microsomal triglyceride transfer protein (MTP) catalyzes the assembly of triglyceride (TG)-rich apolipoprotein B-containing liver (e.g., VLDL) and intestinal (e.