ABSTRACT: Transcriptional profiling was used to identify genes and pathways that responded to intracerebroventricular (ICV) injection of melanocortin-4 receptor (MC4R) agonist, NDP-MSH, in pigs homozygous for the missense mutation in the MC4R, D298 allele (n = 12), N298 allele (n = 12) or heterozygous (n = 12). Food intake (FI) was measured at 12 and 24 hr after treatment. All pigs were sacrificed at 24 hr after treament and hypothalamus, liver and backfat tissue was collected. NDP-MSH suppressed (P < 0.004) FI at 12 and 24 hr in all animals after treatment. In response to NDP-MSH, 278 genes in hypothalamus (q </= 0.07, P </= 0.001), 249 genes in liver (q </= 0.07, P </= 0.001) and 5066 genes in fat (q </= 0.07, P </= 0.015) were differentially expressed. Pathway analysis of NDP-MSH-induced differentially expressed genes indicated that genes involved in cell communication, nucleotide metabolism, and signal transduction were prominently down-regulated in the hypothalamus. In both liver and adipose tissue, energy-intensive biosynthetic and catabolic processes were down-regulated in response to NDP-MSH. This included genes encoding for biosynthetic pathways such as steroid and lipid biosynthesis, fatty acid synthesis, and amino acid synthesis. Genes involved in direct energy-generating processes, such as oxidative phosphorylation, electron transport, ATP synthesis were up-regulated, whereas TCA associated genes, were prominently down-regulated in NDP-MSH treated pigs. Our data also indicate a metabolic switch toward energy conservation since genes involved in energy-intensive biosynthetic and catabolic processes were down-regulated in NDP-MSH treated pigs. Key words: pig, MSH, microarray, liver.
Physiological Genomics 03/2010; · 2.73 Impact Factor