Campus Units

Animal Science, Statistics, Bioinformatics and Computational Biology

Document Type

Article

Publication Version

Published Version

Publication Date

5-1-2010

Journal or Book Title

Physiological Genomics

Volume

41

Issue

3

First Page

254

Last Page

268

DOI

10.1152/physiolgenomics.00006.2010

Abstract

Transcriptional profiling was used to identify genes and pathways that responded to intracerebroventricular injection of melanocortin-4 receptor (MC4R) agonist [Nle4, D-Phe7]-α-melanocyte stimulating hormone (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 h after treatment. All pigs were killed at 24 h after treatment, and hypothalamus, liver, and back-fat tissue was collected. NDP-MSH suppressed (P < 0.004) FI at 12 and 24 h 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 5,066 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 downregulated in the hypothalamus. In both liver and adipose tissue, energy-intensive biosynthetic and catabolic processes were downregulated 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, and ATP synthesis, were upregulated, whereas TCA-associated genes were prominently downregulated 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 downregulated in NDP-MSH-treated pigs.

Comments

This article is from Physiological Genomics 41 (2010): 254–268, doi:10.1152/physiolgenomics.00006.2010.

Rights

Works produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted.

Language

en

File Format

application/pdf

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