Identification of fasting-induced genes in the rat hypothalamus: relationship with neuroprotection.

During food shortage, organisms activate defense mechanisms to maximize their chance of survival. At least in part, these responses are triggered by changes in hormonal status and neural status during starvation. The hypothalamus is organized as a collection of distinct autonomously active nuclei and is considered to play crucial roles in these survival responses. To isolate factors involved in these pathways, we carried out suppression subtractive hybridization analyses using complementary DNAs (cDNA) from the hypothalami of fasted and fed rats. We identified four genes, namely ubiquitin-conjugating enzyme E2D 3 (UBE2D3), cAMP-dependent protein kinase C beta subunit (PKCbeta), excitatory amino acid carrier 1 (EAAC1), and ferritin heavy polypeptide 1 (Fth1), that were upregulated after a 48-h fast compared to the fed status. According to previous reports, these genes have been implicated in protection against neuronal cell death under various neurodegenerative stresses, such as hypoxia-ischemia and oxidative stress. Thus, the increased expressions of the genes identified in the present study may have protective effects against neural damage that could otherwise result in cell death.