Hepatic mRNAs up‐regulated by starvation: an expression profile determined by suppression subtractive hybridization

Abstract

ABSTRACT Delineating the molecular basis for the metabolic switch from the well‐fed state to starvation is crucial to understanding nutritionally regulated metabolic abnormalities. We have examined the molecular events associated with nutrient deprivation, using suppression subtractive hybridization to define the transcriptional programs up‐regulated in rat liver by starvation. Of the genes that displayed significant increases in their hepatic mRNA levels following 48‐h starvation, most could be assigned to one of five major functional classes. We found up‐regulation of genes involved in energy and protein metabolism, genes that respond to stress, and genes encoding nutrient transporters or signaling transducers. The genes with functions in energy and protein metabolism have roles in initiating gluconeogenesis, switching fuel sources from carbohydrates to fatty acids, and protein turnover. A variety of stress response genes, including acute‐phase reactants, exhibited a marked increased in expression, indicating an attempt to restore homeostasis. The expression of several integrated membrane nutrient transporters that supply essential metabolic substrates was increased dramatically. Some known cytosolic signal transducers, likely involved in the metabolic shift from an anabolic to a catabolic state and in the stress response, were significantly enhanced as well. We also observed increased expression of a variety of other known and novel genes. Collectively, our findings indicate that starvation stimulates multiple signaling pathways, which likely lead to extensive metabolic alterations in the liver. These data should serve to enhance our understanding of the molecular mechanisms underlying energy and nitrogen expenditure in the starved state.