Transcriptional profiling of chromosome 17 quantitative trait Loci for carbohydrate and total calorie intake in a mouse congenic strain reveals candidate genes and pathways.
OBJECTIVE
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.


CONCLUSIONS
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.
Division of Experimental Obesity, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, La., USA.
K Ganesh
KG
Kumar
Brenda K
BK
Smith Richards
D000818:Animals; D050260:Carbohydrate Metabolism / Q000235:genetics*; D033481:Chromosomes, Mammalian / Q000235:genetics*; D002149:Energy Intake / Q000235:genetics*; D005502:Food; D005518:Food Preferences / Q000502:physiology; D020869:Gene Expression Profiling; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D040641:Quantitative Trait Loci; D015398:Signal Transduction / Q000235:genetics; D015533:Transcriptional Activation / Q000502:physiology