QTL analysis of self-selected macronutrient diet intake: fat, carbohydrate, and total kilocalories

Abstract

The present study investigated the inheritance of dietary fat, carbohydrate, and kilocalorie intake traits in an F(2) population derived from an intercross between C57BL/6J (fat-preferring) and CAST/EiJ (carbohydrate-preferring) mice. Mice were phenotyped for self-selected food intake in a paradigm which provided for 10 days a choice between two macronutrient diets containing 78/22% of energy as a composite of either fat/protein or carbohydrate/protein. Quantitative trait locus (QTL) analysis identified six significant loci for macronutrient intake: three for fat intake on chromosomes (Chrs) 8 (Mnif1), 18 (Mnif2), and X (Mnif3), and three for carbohydrate intake on Chrs 17 (Mnic1), 6 (Mnic2), and X (Mnic3). An absence of interactions among these QTL suggests the existence of separate mechanisms controlling the intake of fat and carbohydrate. Two significant QTL for cumulative kilocalorie intake, adjusted for baseline body weight, were found on Chrs 17 (Kcal1) and 18 (Kcal2). Without body weight adjustment, another significant kcal locus appeared on distal Chr 2 (Kcal3). These macronutrient and kilocalorie QTL, with the exception of loci on Chrs 8 and X, encompassed chromosomal regions influencing body weight gain and adiposity in this F2 population. These results provide new insight into the genetic basis of naturally occurring variation in nutrient intake phenotypes.

Genetic variation inGlp1rexpression influences the rate of gastric emptying in mice

“…Animals, breeding, and phenotyping protocols used in the genetic mapping study are described in detail elsewhere (46). Microsatellite-assisted selection at every generation was used to develop a speed congenic line, B6.CAST D17Mit19-D17Mit91 (B6.CAST-17) (26).…”

“…A genome scan with 98 Mit SSLP markers at ϳ20-cM intervals was performed in 502 mice (46) using the method of Sen and Churchill (45) with Pseudomarker release version 1.06, available at http://www.jax.org/staff/ churchill/labsite. Significance was assessed by permutation analysis (10); the log of the odds ratio (LOD) threshold for significant linkage was 3.5.…”

“…Thus we conducted a genome scan for this phenotype in a mapping population used previously (46). Genome scans for total food volume (g) over the 10-day phenotyping period, with and without baseline body weight as a covariate, are presented in Fig.…”

“…Glp1r maps to the peak of a genetic region containing overlapping quantitative trait loci (QTL) for carbohydrate intake (Mnic1) and total calorie intake (Kcal2) on proximal chromosome 17 (46), mapped using a C57BL/6J (B6) ϫ CAST/Ei (CAST) intercross. These coincident QTL suggest that a common gene may be contributing to both traits.…”

“…In this regard, the parental CAST and B6.CAST-17 congenic mice select/consume more carbohydrate and total energy per body weight (26), and thus higher food volume, when compared with B6. To uncover the genetic loci involved in total food volume, we conducted a genome scan for 10-day consumption (g) in an existing mapping population (46). Finally, although Glp1r is an obvious positional candidate, the congenic interval on chromosome 17 contains a large number of genes.…”