Kellie A. Rance

Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure.

The FTO gene has significant polymorphic variation associated with obesity, but its function is unknown. We screened a population of 150 whites (103F/47M) resident in NE Scotland, United Kingdom, for variants of the FTO gene and linked these to phenotypic variation in their energy expenditure (basal metabolic rate (BMR) and maximal oxygen consumption VO2max) and energy intake. There was no significant association between the FTO genotype and BMR or VO2max. The FTO genotype was significantly associated (P = 0.024) with variation in energy intake, with average daily intake being 9.0 MJ for the wild‐type TT genotype and 10.2 and 9.5 MJ for the “at risk” AT and AA genotypes, respectively. Adjusting intake for BMR did not remove the significance (P = 0.043). FTO genotype probably affects obesity via effects on food intake rather than energy expenditure.

Additional anthropometric measures may improve the predictability of basal metabolic rate in adult subjects

Background:The most commonly used predictive equation for basal metabolic rate (BMR) is the Schofield equation, which only uses information on body weight, age and sex to derive the prediction. However, because body composition is a key influencing factor, there will be error in calculating an individuals basal requirements based on this prediction.Objective:To investigate whether adding additional anthropometric measures to the standard measures can enhance the predictability of BMR and to cross-validate this within a separate subgroup.Design:Cross-sectional study of 150 Caucasian adults from Scotland, with a body mass index range of 16.7–49.3 kg/m2. All subjects underwent measurement of BMR, body composition, and 148 also had basic skinfold and circumference measures taken. The resultant equation was tested in a subgroup of 39 obese males.Results:The average difference between the predicted (Schofield equation) and measured BMR was 502 kJ/day. There was a slight systematic bias in this error, with the Schofield equation underestimating the lowest values. The average discrepancy between predicted and actual BMR was reduced to 452 kJ/day, with the addition of fat mass, fat-free mass, an overall 10% improvement on the Schofield equation (P=0.054). Using an equation derived from principal components analysis of anthropometry measurements similarly decreased the difference to 458 kJ/day (P=0.039). Testing the equation in a separate group indicated a 33% improvement in predictability of BMR, compared to the Schofield equation.Conclusions:In the absence of detailed information on body composition, utilizing anthropometric data provides a useful alternative methodology to improve the predictability of BMR beyond that achieved from the standard Schofield prediction equation. This should be confirmed in more individuals, both within the obese and normal weight category.

A QTL affecting daily feed intake maps to Chromosome 2 in pigs

Our understanding of the molecular genetic basis of several key performance traits in pigs has been significantly advanced through the quantitative trait loci (QTL) mapping approach. However, in contrast to growth and fatness traits, the genetic basis of feed intake traits has rarely been investigated through QTL mapping. Since feed intake is an important component of efficient pig production, the identification of QTL affecting feed intake may lead to the identification of genetic markers that can be used in selection programs. In this study a QTL analysis for feed intake, feeding behavior, and growth traits was performed in an F2 population derived from a cross between Chinese Meishan and European Large White pigs. A QTL with a significant effect on daily feed intake (DFI) was identified on Sus scrofa Chromosome 2 (SSC2). A number of suggestive QTL with effects on daily gain, feed conversion, and feeding behavior traits were also located. The significant QTL lies close to a previously identified mutation in the insulin-like growth factor 2 gene (IGF2) that affects carcass composition traits, although the IGF2 mutation is not segregating in the populations analyzed in the current study. Therefore, a distinct causal variant may exist on the P arm of SSC2 with an effect on feed intake.

Plasma leptin levels are related to body composition, sex, insulin levels and the A55V polymorphism of the UCP2 gene

Objective:Circulating leptin levels show a high degree of individual variability even after the main effect of body fatness is accounted for. We therefore wanted to determine the roles of variation in body composition, age, sex and polymorphisms of the UCP2 gene and promoter region on levels of circulating leptin.Subjects:One hundred and fifty Caucasian subjects, which represented a cross-section of the population from NE, Scotland, were recruited.Measurements:Body composition was measured using dual X-ray absorptiometry. Fasted circulating leptin, insulin, T3 and T4 levels were measured, and all individuals were genotyped for the UCP2 polymorphisms A55V, –866G>A and exon-8 ins/del.Results:The results indicate that circulating leptin was significantly related to sex and principle component (PC) scores representing overall adipose tissue mass and a second representing the contrast of central to peripheral bone mineral content. Residual leptin was associated with the A55V polymorphism (P< 0.001) explaining 11.3% of the residual variance. There was a marginal effect associated with exon-8 ins/del (P=0.045) explaining 4.4% of the residual variance in leptin. Loge transformed circulating fasting insulin was related to PC scores representing general adiposity and sex. Residual Loge insulin was associated with the A55V and exon-8 ins/del polymorphisms explaining 5.7% (P=0.015) and 5% (P=0.026) of the residual variation, respectively. The –866G>A polymorphism was not significantly associated with residual leptin or insulin. Leptin and insulin were significantly (P=0.007) correlated. Statistically removing the effect of insulin on leptin still showed association between leptin and A55V (P=0.002). Removing the effect of leptin on insulin, the A55V polymorphism was no longer significant (P=0.120). After accounting for the correlation between insulin and leptin, the exon-8 ins/del was no longer significant for residual leptin (P=0.119) or Loge insulin (P=0.252).Conclusion:These data suggest that the A55V polymorphism directly affected the levels of leptin but not via an effect on insulin.

A polymorphism in the 5'-untranslated region of the porcine cholecystokinin type a receptor gene affects feed intake and growth.

The location and utilization of quantitative trait loci (QTL) and candidate genes with significant effects on economically important traits are becoming increasingly important in livestock breeding programs. The porcine cholecystokinin type A receptor (CCKAR) is a candidate gene for performance traits, due to its known role in the physiological control of feed intake, satiety, and obesity. We investigated the association of CCKAR polymorphisms with feeding, growth, and efficiency traits in an F2 population derived from a cross between Meishan and Large White founder animals and in lines of Large White pigs that had been divergently selected on the basis of lean growth efficiency traits. In the F2 population, CCKAR genotype was significantly associated with daily feed intake and average daily gain. The effects of the polymorphisms were then assessed in a larger-scale analysis of segregating commercial lines. A newly discovered single-nucleotide polymorphism (SNP) within the 5′-untranslated region (5′-UTR) had highly significant effects on feed intake, average daily gain, and days to 110 kg, which were not seen for a previously reported SNP within the CCKAR gene. Furthermore, we provide evidence that the novel SNP disrupts the binding of the YY1 transcription factor, which raises the possibility that it is the causal variant. The 5′-UTR SNP could be utilized as a molecular genetic test for increased feed intake, faster lean growth, and reduced days to market weight in segregating commercial lines.

A paternally imprinted QTL for mature body mass on mouse Chromosome 8

Body mass (BM) is a classic polygenic trait that has been extensively investigated to determine the underlying genetic architecture. Many previous studies looking at the genetic basis of variation in BM in murine animal models by quantitative trait loci (QTL) mapping have used crosses between two inbred lines. As a consequence it has not been possible to explore imprinting effects which have been shown to play an important role in the genetic basis of early growth with persistent effects throughout the growth curve. Here we use partially inbred mouse lines to identify QTL for mature BM by applying both Mendelian and Imprinting models. The analysis of an F2 population (n ≈ 500) identified a number of QTL at 14, 16, and 18 weeks explaining in total 31.5%, 34.4%, and 30.5% of total phenotypic variation, respectively. On Chromosome 8 a QTL of large effect (14% of the total phenotypic variance at 14 weeks) was found to be explained by paternal imprinting. Although Chromosome 8 has not been previously associated with imprinting effects, features of candidate genes within the QTL confidence interval (CpG islands and direct clustered repeats) support the hypothesis that Insulin receptor substrate 2 may be associated with imprinting, but as yet is unidentified as being so.

Evaluating energy intake measurement in free-living subjects: when to record and for how long?

OBJECTIVE To nutritionally analyse mean energy intake (EI) from different 3 d intervals within a 7 d recording period and to evaluate the seasonal effect on energy and nutrient intake. DESIGN Cross-sectional study of dietary intake collected with 7 d food diaries. SETTING Aberdeen, north-east Scotland, UK, between 2002 and 2004. SUBJECTS Participants from two long-term trials were pooled. These trials, investigating genetic and environmental influences on body weight, were the Genotyping And Phenotyping (GAP) study and a cohort observational study, Rowett Assessment of Childhood Appetite and metaboLism (RASCAL). There were 260 Caucasian adults, BMI range 16.7-49.3 kg/m2, age range 21-64 years. RESULTS Mean EI for Wednesday, Friday and Saturday had the closest approximation to the 7 d mean (0.1 % overestimate). A gender x season interaction (P = 0.019) with a different intake pattern for females and males was observed. For females, lower mean (se) EI was recorded in summer (8117 (610) kJ) and autumn (7941 (699) kJ) compared with spring (8929 (979) kJ) and winter (8132 (1041) kJ). For males, higher mean (se) EI was recorded in summer (10 420 (736) kJ) and autumn (10 490 (1041) kJ) compared with spring (9319 (1441) kJ) and winter (9103 (1505) kJ). CONCLUSIONS The study results indicate that 3 d weighed intakes recorded from Wednesday, Friday and Saturday are most representative of 7 d habitual intake in free-living subjects. They also indicate that seasonality has a limited effect on EI and no effect on macronutrient intake.

Quantitative Trait Loci for Regional Adiposity in Mouse Lines Divergently Selected for Food Intake

Objective: Obesity is thought to result from an interaction between genotype and environment. Excessive adiposity is associated with a number of important comorbidities; however, the risk of obesity‐related disease varies with the distribution of fat throughout the body. The aim of this study was to map quantitative trait loci (QTLs) associated with regional fat depots in mouse lines divergently selected for food intake corrected for body mass.