Transcriptional Profiling of Chromosome 17 Quantitative Trait Loci for Carbohydrate and Total Calorie Intake in a Mouse Congenic Strain Reveals Candidate Genes and Pathways

• Published in: Journal of nutrigenetics and nutrigenomics Vol. 1; no. 4; pp. 155 - 171
• Main Authors: Kumar, K. Ganesh, Smith Richards, Brenda K.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland 01.01.2008
• Subjects: Animals; Carbohydrate Metabolism - genetics; Chromosomes, Mammalian - genetics; Energy Intake - genetics; Food; Food Preferences - physiology; Gene Expression Profiling; Mice; Mice, Congenic; Mice, Inbred C57BL; Models, Biological; Oligonucleotide Array Sequence Analysis; Original Paper; Phenotype; Quantitative Trait Loci; Signal Transduction - genetics; Transcriptional Activation - physiology; Congenic; Microarray; Food intake; Mouse chromosome 17; QTL mapping
• ISSN: 2504-3161; 1661-6499; 2504-3188
• DOI: 10.1159/000113657

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.