Regulation of hepatic gene expression by lipogenic diet and thyroid hormone.

Adaptive hyperlipogenesis in the liver occurs after feeding rats a high-carbohydrate, fat-free diet or after treatment with thyroid hormone. This phenomenon is accompanied by the induction of a family of enzymes and proteins involved in various aspects of lipogenesis, resulting largely from alterations in the rates of protein synthesis. The changes in protein production, in turn, are the result of increased or decreased cellular concentrations of specific mRNAs in response to carbohydrate feeding or hyperthyroidism. There is a large degree of overlap between the mRNA species induced by thyroid hormone and carbohydrate feeding in rat liver. One such mRNA species, spot 14, has several attractive features as a potential model for exploring the molecular mechanisms involved in the regulation of gene expression. Most importantly, the mRNA for spot 14 increases with a lag time of less than 20 min after treatment with thyroid hormone or sucrose gavage and thus may represent a primary response to the hormonal and dietary stimuli. Initial studies to elucidate the cellular site of action of thyroid hormone and dietary carbohydrate indicate that changes in both the rate of gene transcription and the stability of the nuclear RNA precursor are involved in spot 14 mRNA induction.