II-83Posters
CROSS SPECIES SURVEY STUDY OF POTENTIAL
PHARMACOLOGICAL TARGETS FOR ANTI-OBESITY DRUGS
Tanja Kunej1, Peter Dovč1, Jennifer J. Michal2, Zhihua Jiang2
1 Department of Animal Science, University of Ljubljana, Domžale, Slovenia
2 Department of Animal Sciences, Washington State University, Pullman, WA, USA;
tanja.kunej@bfro.uni-lj.si
Introduction Obesity and obesity related conditions represent a leading public health problem in devel-
oped countries. Studies have shown that insulin resistance affiliated with obesity is associ-
ated with intramyocellular lipid (IMCL) accumulation.1 Therefore, identification of genes
associated with fat deposition would provide a promising target for pharmaceutical inter-
vention and care for the condition. There are currently more than 600 loci in the human
obesity gene map, comprising of gene candidates from animal models, association studies
and QTL mapping experiments.2 Here we review research on candidate genes that were
shown to be associated with fat deposition by our studies and used comparative genomics
approach for their further confirmation as potential pharmacological targets for anti-obe-
sity drugs.
Material and Genomic organization of cattle gene candidates for fat deposition was determined using
methods in silico cloning approach and sequencing of their promoter- and coding regions. The
developed markers were tested on an unique animal genetic resource, 250 Wagyu × Lim-
ousin F2 progeny from the cross of two cattle breeds with extreme phenotypes informative
for IMCL and subcutaneous fat depth (SFD) developed at Washington State University and
USDA, ARS.
Results Nine genes were associated with IMCL and/or SFD.3–7 The candidate gene list and estima-
tions of phenotypic effects of different alleles are presented in Table 1. All nine candidate
genes reside in previously detected and published QTL regions/concordant QTL regions.
For eight genes, involvement in fat associated traits was confirmed in other mammalian
species (2,8, PubMed Database).
Table 1. Genes associated with IMCL and/or SFD in Wagyu × Limousin F2 progeny.
Gene/ IMCL (number of SFD (number of Gene in QTL/concordant Cross species
markers SNPs associated) SNPs associated) QTL region identification of fat associated traits
TFAM 3 (promoter) 2 (promoter) SSC14 pig, mouse
UCN3 2* (exon 2) 4* (promoter) HSA10p15.1 rat
FABP4 1 1 BTA14, SSC4 pig, mouse
PAPD1 – 2 (promoter) HSA10p11.23 –
TG – 1 BTA14 mouse
LEP – 1 (exon 2) HSA7q3, BTA4q human, mouse
DGAT1 – 1 BTA14 mouse
GH1 – 1 (intron 3) BTA19 human, mouse
FABP3 – 1 SSC6q pig, mouse
TFAM: mitochondrial transcription factor A, UCN3: urocortin 3, FABP4: Fatty acid binding protein 4, PAPD1: mitochon-
drial poly(A) polymerase, TG: thyroglobulin, LEP: leptin, DGAT: Diacyglycerol O-acyltransferase 1, GH1: growth hor-
mone 1, FABP3: fatty acid binding protein (heart) 3, *SNPs in linkage disequilibrium.
Conclusions Our multi species survey study revealed evidence for nine genes that are involved in obesi-
ty related phenotypes and therefore could be proposed as potential targets for anti-obesity
drug development.
References
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