Arcuate Nucleus Transcriptome Profiling Identifies Ankyrin Repeat and Suppressor of Cytokine Signalling Box-Containing Protein 4 as a Gene Regulated by Fasting in Central Nervous System Feeding Circuits

The arcuate nucleus of the hypothalamus is a primary site for sensing blood borne nutrients and hormonal messengers that reflect caloric status. To identify novel energy homeostatic genes, we examined RNA extracts from the microdissected arcuate nucleus of fed and 48‐h fasted rats using oligonucleotide microarrays. The relative abundance of 118 mRNA transcripts was increased and 203 mRNA transcripts was decreased during fasting. One of the down‐regulated mRNAs was ankyrin‐repeat and suppressor of cytokine signalling box‐containing protein 4 (Asb‐4). The predicted structure of Asb‐4 protein suggested that it might encode an intracellular regulatory protein, and therefore its mRNA expression was investigated further. Reverse transcription quantitative polymerase chain reaction was used to validate down‐regulation of Asb‐4 mRNA in the arcuate nucleus of the fasted Sprague‐Dawley rat (relative expression of Asb‐4 mRNA: fed = 4.66 ± 0.26; fasted = 3.96 ± 0.23; n = 4, P