Characterization of the hypothalamic transcriptome in response to food deprivation reveals global changes in long noncoding RNA, and cell cycle response genes

Abstract

The hypothalamus integrates energy balance information from the periphery using different neuronal subtypes within each of the hypothalamic areas. However, the effects of prandial state on global mRNA, microRNA and long noncoding (lnc) RNA expression within the whole hypothalamus are largely unknown. In this study, mice were given either a 24-h fast, or ad libitum access to food. RNA samples were analyzed by microarray, and then a subset was confirmed using quantitative real-time PCR (QPCR). A total of 540 mRNAs were either up-or down-regulated with food deprivation. Since gene ontology enrichment analyses identified several categories of mRNAs related to cell cycle processes, ten cell-cycle-re-lated genes were further analyzed using QPCR with six confirmed to be significantly up-regulated and one down-regulated in response to 24-h fasting. While 22 independent microRNAs were differentially expressed by microarray, secondary analysis by QPCR failed to confirm significant changes with fasting. There were 622 lncRNAs identified as differentially expressed, and of three tested by QPCR, two were confirmed. Overall, this is the first time that expression of hypothalamic lncRNAs has been shown to be responsive to food deprivation. In addition, this study is the first to identify a list of lncRNAs with high expression in RNA extracted from hypothalamus. Individual contribu-tions from specific miRNA, lncRNA and mRNAs to the food deprivation response can now be further studied at the physiological and biochemical levels.