To achieve the target rate of lean mass accretion set by photoperiod, it is implied that food intake is adjusted to match the protein requirements for growth. On a HFD, rats reduce their food intake, which suggests that protein uptake and assimilation must be more efficient on a HFD than on a chow diet. Nonetheless energy intake is increased leading to greater deposition of adipose tissue. This rebalancing of food intake, energy intake and protein intake, without overt effects on genes involved in the hypothalamic energy balance circuits, indicates that factors other than leptin must be involved in determining this new equilibrium when animals are placed on a HFD. By contrast a HFD exerts a suppressive effect on the growth axis at the level of the hypothalamus, and it appears that these effects are independent of the photoperiod regulatory mechanisms. The effects on GHRH appear to be an early effect of a HFD on the somatotrophic axis and it seems likely that overt effects on serum IGF-1 levels and lean mass accretion will only be seen after prolonged exposure to a HFD. Forward genetic A 85380 dihydrochloride screens are a powerful means to decipher a biological process without any prior knowledge or 5-Fluoroorotic acid assumptions. Typically such screens are performed in yeast, Drosophila, Caenorhabditis elegans and other genetic model organisms to identify new gene functions. Application of this method to human cultured cells allows the dissection of pathways that are dissimilar or even absent in other model organisms. It may also enable the discovery of novel drug targets to treat disease. Genetic screens in human cells have been limited by the difficulties inherent in revealing recessive phenotypes in diploid cells. While RNAi screens have been an important advance, they are complicated by off-target effects and often do not completely eliminate the relevant gene product. The recent isolation of human cells lines that are nearly or completely haploid has revolutionized human forward genetic screens and led to the identification of numerous human host factors required for infection by pathogens and intoxication by bacterial toxins. The majority of human haploid screens reported to date have involved the selection of mutants that are resistant to an agent that is lethal to wild-type cells. The one exception is a recent screen that used fluorescence activated-cell sorting to identify genes involved in MHC class I antigen presentation by sorting for mutants that were defective in surface expression of MHC-1. We sought to further expand the types of biological pathways that can be studied using human haploid genetic screens by using a transcriptional reporter in conjunction with selection for a lethal phenotype. Transcription factors often lie at the terminus of complex signaling pathways and control gene transcription programs that regulate diverse processes, ranging from proliferation, differentiation, apoptosis, immune response, to metabolism.