Gene expression in hypothalamus, liver, and adipose tissues and food intake response to melanocortin-4 receptor agonist in pigs expressing melanocortin-4 receptor mutations

Date
2010-05-01
Authors
Barb, C. Richard
Hausman, Gary
Rekaya, Romdhane
Lents, Clay
Lkhagvadorj, Sender
Qu, Long
Cai, Weiguo
Couture, Oliver
Anderson, Lloyd
Dekkers, Jack
Tuggle, Christopher
Major Professor
Advisor
Committee Member
Journal Title
Journal ISSN
Volume Title
Publisher
Altmetrics
Authors
Research Projects
Organizational Units
Animal Science
Organizational Unit
Statistics
Organizational Unit
Journal Issue
Series
Department
Animal ScienceStatisticsBioinformatics and Computational Biology
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.

Description
Keywords
Citation
DOI
Collections