Transcriptional profiling of chromosome 17 quantitative trait Loci for carbohydrate and total calorie intake in a mouse congenic strain reveals candidate genes and pathways.
J Nutrigenet Nutrigenomics, 2008;1(4):155-71.
Kumar KG[1], Smith Richards BK
Affiliations
PMID: 19776624DOI: 10.1159/000113657
Abstract
background/aims: The genetic basis for ingestive behaviors is virtually unknown. Quantitative trait loci (QTLs) for carbohydrate and energy intake map to mouse chromosome 17 and were previously confirmed by a congenic strain bearing CAST/Ei (CAST) donor segment on the C57BL/6J (B6) background.
methods: We used microarray technology to facilitate gene identification. Gene expression was compared between the B6.CAST-17 (BC-17) congenic and B6 strains in two diets: (1) chow, and (2) carbohydrate/protein vs. fat/protein.
results: Within the QTL and unique to macronutrient selection, Agpat1 (acylglycerol-3-phosphate O-acyltransferase 1) was differentially expressed in hypothalamus. Irrespective of diet, the gene with the highest fold difference in congenic mice was trefoil factor 3 (Tff3) in liver. Several genes involved in fat metabolism were decreased in carbohydrate-preferring congenic mice, while genes associated with carbohydrate metabolism were increased. In particular, the glyoxalase pathway was enhanced including Glo1, Glo2, and dLDH. Higher expression of Glo1 mRNA in BC-17 congenic mice corresponded to increased protein expression revealed by Western blot, and to higher GLO1 activity in blood.
conclusion: These genes represent new candidates for nutrient intake phenotypes. We propose that increased GLO1 in the BC-17 strain supports its need to protect against dietary oxidants resulting from high carbohydrate intake.
MeSH terms
Animals; Carbohydrate Metabolism; Chromosomes, Mammalian; Energy Intake; Food; Food Preferences; Gene Expression Profiling; Mice; Mice, Congenic; Mice, Inbred C57BL; Models, Biological; Oligonucleotide Array Sequence Analysis; Phenotype; Quantitative Trait Loci; Signal Transduction; Transcriptional Activation
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