Contents lists available at ScienceDirect Comparative Biochemistry and Physiology - Part D journal homepage: www.elsevier.com/locate/cbpd Whole brain transcriptomics of intermittently fed individuals of the marine teleost Sparus aurata O. Ntantali a, , E.E. Malandrakis b , W. Abbink c , E. Golomazou a , I.T. Karapanagiotidis a , H. Miliou b , P. Panagiotaki a a Department of Ichthyology and Aquatic Environment, School of Agricultural Sciences, Fitokou str., 38445 Volos, Greece b Department of Animal Science, School of Animal Biosciences, Agricultural University of Athens, Iera Odos 75, 11855 Athens, Greece c Animal Breeding & Genomics, Wageningen Livestock Research, Wageningen University and Research, Droevendaalsesteeg 1, Wageningen, the Netherlands ARTICLEINFO Keywords: Intermittent feeding Brain transcriptome RNA-seq Ion transport ABSTRACT A major challenge in fish physiology is to understand the mechanisms underlying the transcriptomic responses of fish brain to food deprivation. Differential gene expression analysis identified in total 2240 transcripts that presented > 2-fold change (adjusted p < 0.01) between each treatment and the control group (C). The identity of the transcripts was obtained with annotation against multiple public databases and they were grouped ac- cording to their expression patterns. The gene ontology terms that were substantially affected were identified by functional annotation analysis. Genes related to ion transport, cell cycle and cell adhesion were mainly regulated during fasting and refeeding. These findings contribute to identify key indicators for the molecular basis of brain functions during periods of starvation in gilthead seabream. 1. Introduction Fish in nature often go through long periods of food deprivation due to seasonal changes, lack of prey and reproduction, so that their me- tabolism is evolutionary adapted to long fasting periods (Midwood et al., 2016; Kennedy et al., 2017). Besides natural populations the understanding of the nutritional physiology under food deprivation periods, is of paramount importance for the aquaculture industry (Nicieza and Metcalfe, 1997; Johansen et al., 2001; Foss et al., 2009). Food restriction is often practiced in aquaculture in order to reduce feed and feeding costs, as well as environmental impact (Maciel et al., 2018). Furthermore, feed restriction is usually applied to laboratory fish as common practice during experimental routines. It is not well known if fish perceive hunger as mammals do; holistic gene expression ap- proaches can shed light towards this query. Teleosts comprise a diverse group of fish in terms of diet, feeding habits and nutritional physiology. Therefore, molecular systems underlying feeding behavior and nutri- tional physiology are considered to be inconsistent among different species. Food restriction triggers hormonal and neuronal responses that tend to maintain metabolism and energy balance in fish (Bertucci et al., 2019). The brain receives and handles both external and peripheral stimuli related to food intake. Therefore, any food deprivation is per- ceived by the central nervous system. Depending on its severity (period and amount of available food), fasting may affect many physiological functions, such as development, growth, reproduction, digestion, os- moregulation and stress-coping (Polakof et al., 2006; Inness and Metcalfe, 2008; Davis and Gaylord, 2011; Pikle et al., 2017). In previous studies, the impact of fasting on brain physiology has been investigated in various fish species. Brain regulates fish appetite in a manner that increases or inhibits feeding by hormones (reviewed by Volkoff, 2016). Fasting increased the expression of both the orexigenic and anorexigenic hormones in glass catfish (Kryptopterus vitreolus), but decreased the major reproductive peptide GnRH1 (London and Volkoff, 2019). Yang et al. (2019) studied the brain transcriptome of the freshwater species Spinibarbus hollandi, and concluded that fish mobi- lize energy and reduce demands to prolong survival during fasting, while inducing ribosomal protein, stimulus response, and carbohydrate metabolism towards eliminating negative effects of starvation on brain. So far, to our knowledge, studies of brain transcriptomics during food restriction are scarce for marine fish species, and can provide in- formation on physiological aspects during periods of food limitation. Towards this goal, gilthead seabream (Sparus aurata) was used as a major Mediterranean aquaculture species. We performed global gene expression profiling of whole sea bream brains. Genome-wide tran- scriptome changes were assessed in both starved and re-fed specimens. Profiles of genome-wide transcriptome changes were carried out at https://doi.org/10.1016/j.cbd.2020.100737 Received 20 April 2020; Received in revised form 16 July 2020; Accepted 15 August 2020 Corresponding author. E-mail address: ntolga@uth.gr (O. Ntantali). Comparative Biochemistry and Physiology - Part D 36 (2020) 100737 Available online 21 August 2020 1744-117X/ © 2020 Elsevier Inc. All rights reserved. T