Gene expression in hypothalamus, liver and adipose tissues and feed intake response to melanocortin-4 receptor (MC4R) agonist in pigs expressing (MC4R) mutations
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1
Russell Research Center, USDA-ARS, United States
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2
University of Georgia, Department of Animal and Dairy Science, United States
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3
Iowa State University, Department of Animal Science, United States
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). Feed 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 ï‚£ 0.07, P ï‚£ 0.001), 249 genes in liver (q ï‚£ 0.07, P ï‚£ 0.001) and 5066 genes in fat (q ï‚£ 0.07, P ï‚£ 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.
Conference:
2010 South East Nerve Net (SENN) and Georgia/South Carolina Neuroscience Consortium (GASCNC) conferences, Atlanta , United States, 5 Mar - 7 Mar, 2010.
Presentation Type:
Poster Presentation
Topic:
Posters
Citation:
Barb
RC,
Hausman
GJ,
Rekaya
R,
Lents
CA,
Lkhagvadorj
S,
Qu
L,
Cai
W,
Couture
OP,
Anderson
LL,
Dekkers
JC and
Tuggle
CK
(2010). Gene expression in hypothalamus, liver and adipose tissues and feed intake response to melanocortin-4 receptor (MC4R) agonist in pigs expressing (MC4R) mutations.
Front. Neurosci.
Conference Abstract:
2010 South East Nerve Net (SENN) and Georgia/South Carolina Neuroscience Consortium (GASCNC) conferences.
doi: 10.3389/conf.fnins.2010.04.00023
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Received:
15 Mar 2010;
Published Online:
15 Mar 2010.
*
Correspondence:
Richard C Barb, Russell Research Center, USDA-ARS, Athens, United States, richard.barb@ars.usda.gov