Direct evidence for a role of the "spot 14" protein in the regulation of lipid synthesis.

摘要: "Spot 14" is a nuclear protein that rapidly induced by thyroid hormone (T3) and dietary carbohydrate in liver. We used an antisense oligonucleotide to inhibit induction of spot 14 T3 glucose primary cultures rat hepatocytes test the hypothesis could function regulation lipid synthesis. Spot was undetectable maintained 5.5 mM without T3, within 4 h after addition 27.5 50 nM culture medium, reaching maximal level 24 h. Accumulation markedly inhibited transfected with oligonucleotide, but not those treated control oligonucleotide. Transfection antisense, control, also abrogated increase lipogenesis glucose. Reduced triglyceride formation accounted for diminished net In contrast lipogenesis, uptake significantly affected transfections. Antisense transfection both ATP-citrate lyase fatty acid synthase immunoreactivities, as well malic enzyme activity, indicating observed reduction be explained cellular content lipogenic enzymes. activity antisense-transfected accompanied lowered relative abundance mRNA, suggesting effects on enzymes were mediated at pretranslational level. The oligonucleotides did affect hepatoma cell line does express detectable mRNA or protein. These data directly implicate transduction hormonal signals increased metabolism hepatocytes.