A cluster of variants in the fat mass and obesity-associated (FTO) gene are associated with the common form of obesity. Well-documented dietary data are required for identifying how the genetic risk can be modified by dietary factors. The objective of the present study was to investigate the associations between the FTO risk allele (rs9939609) and dietary intake, and to evaluate how dietary intake affects the association between FTO and BMI in the Finnish Diabetes Prevention Study during a mean follow-up of 3
2 years. A total of 479 (BMI >25 kg/m2) men and women were genotyped for rs9939609. The participants completed a 3 d food record at baseline and before every annual study visit. The average intakes at baseline and during the years 1, 2 and 3 were calculated. At baseline, the FTO variant rs9939609 was not associated with the mean values of total energy intake, macronutrients or fibre. At baseline, a higher BMI by the FTO risk genotype was detected especially in those who reported a diet high in fat with mean BMI of 30
6 (sd 4
3 (sd 4
6) and 34
5 (sd 6
2) kg/m2 for TT, TA and AA carriers, respectively (P =0
005). Higher BMI was also observed in those who had a diet low in carbohydrates (P =0
028) and fibre (P =0
015). However, in the analyses adjusted for total energy intake, age and sex, significant interactions between FTO and dietary intakes were not found. These findings suggest that the association between the FTO genotype and obesity is influenced by the components of dietary intake, and the current dietary recommendations are particularly beneficial for those who are genetically susceptible for obesity.
Hypothalamic energy balance genes have been examined in the context of seasonal body weight regulation in the Siberian hamster. Most of these long photoperiod (LD)/short photoperiod (SD) comparisons have been of tissues collected at a single point in the light-dark cycle. We examined the diurnal expression profile of hypothalamic genes in hamsters killed at 3-h intervals throughout the light-dark cycle after housing in LD or SD for 12 wk. Gene expression of neuropeptide Y, agouti-related peptide, proopiomelanocortin, cocaine- and amphetamine-regulated transcript, long-form leptin receptor, suppressor of cytokine signaling-3, melanocortin-3 receptor, melanocortin-4 receptor, and the clock gene Per1 as control were measured by in situ hybridization in hypothalamic nuclei. Effects of photoperiod on gene expression and leptin levels were generally consistent with previous reports. A clear diurnal variation was observed for Per1 in the suprachiasmatic nucleus in both photoperiods. Temporal effects on expression of energy balance genes were restricted to long-form leptin receptor in the arcuate nucleus and ventromedial nucleus, where similar diurnal expression profiles were observed, and melanocortin-4 receptor in the paraventricular nucleus; these effects were only observed in LD hamsters. There was no variation in serum leptin concentration. The 24-h profiles of hypothalamic energy balance gene expression broadly confirm photoperiodic differences that were observed previously, based on single time point comparisons, support the growing consensus that these genes have a limited role in seasonal body weight regulation, and further suggest limited involvement in daily rhythms of food intake.
The glutamate decarboxylase 2 (GAD2) gene encodes for the glutamic acid decarboxylase enzyme (GAD65), which is implicated in the formation of the gamma-aminobutyric acid (GABA), a neurotransmitter involved in the regulation of food intake. The objective of the present study was to test for association between GAD2 single-nucleotide polymorphisms (SNPs) and eating behaviors, dietary intake and obesity in subjects (n=873) from the Quebec Family Study (QFS). Energy and macronutrient intakes were measured using a 3-day dietary record and eating behaviors were assessed using the Three-Factor Eating Questionnaire (TFEQ). Six SNPs capturing about 90% of GAD2 gene variability were genotyped and tested for association with age- and BMI- adjusted phenotypes. No evidence of association was found in men. In women, a SNP (rs992990; c.61450 C>A) was associated with disinhibition (p=0.028), emotional susceptibility to disinhibition (p=0.0005) and susceptibility to hunger (p=0.028). Another SNP (rs7908975; c.8473A>C) was associated with carbohydrate (p=0.021) and lipid (p=0.021) intakes, disinhibition (p=0.011) and two of its subscales (emotional and situational susceptibility) as well as with avoidance of fattening foods (p=0.036). Six-year weight gain was two times higher in women carrying the variants associated with eating behaviors: 4.2kg (vs 2.1kg in non-carriers) in A-allele carriers of c.61450 C>A (p=0.038) and 4.9kg (vs 2.5kg in non-carriers) in C-allele carriers of c. 8473 A>C (p=0.013). The results suggest a role for the GAD2 gene in determining food intake, eating behaviors and weight gain over time in women.
Few twin studies have examined nutrition-related phenotypes among children, and none has investigated energy and macronutrient intakes.
The objective was to quantify genetic and environmental influences on variations in energy and macronutrient intakes among children aged 9 years.
We conducted a nutrition study among children participating in the Quebec Newborn Twin Study, a population-based birth cohort of twins. We derived dietary data from two multiple-pass 24-hour dietary recalls with a parent and his or her child. The analysis employed a classic twin study design and used data from 379 twin pairs.
Univariate analyses indicate that heritability for mean daily energy (kcal) and macronutrient (g) intakes was moderate, ranging from 0.34 (95% CI: 0.22, 0.46) to 0.42 (0.31, 0.53). Genetic effects also accounted for 0.28 (0.16, 0.40) of the variance in percent of energy from lipids, while only environmental (shared and unique) effects accounted for the variance in percent of energy from proteins and carbohydrates. The shared environment did not contribute to variations in daily intakes for most of the nutritional variables under study. Multivariate analyses suggest the presence of macronutrient-specific genetic influences for lipids and carbohydrates, estimated at 0.12 (0.04, 0.19) and 0.20 (0.11, 0.29) respectively.
The unique environment (i.e., not shared by family members) has the largest influence on variances in daily energy and macronutrient intakes in 9-year-old children. This finding underscores the need to take obesogenic environments into account when planning dietary interventions for younger populations.
Eating behaviors during childhood are related both to children's diet quality and to their weight status. A better understanding of the determinants of eating behavior during childhood is essential for carrying out effective dietary interventions.
We assessed the contribution of genetic and environmental factors to variations in selected eating behaviors in early and late childhood. Information on eating behaviors came from questionnaires administered to parents of children participating in the Quebec Newborn Twin Study when the twins were 2.5 and 9 years old (n = 692 children). Dichotomous variables were derived and analyzed using structural equation modeling, as part of a classic twin study design. We performed univariate and bivariate longitudinal analyses to quantify sources of variation and covariation across ages, for several eating behavior traits.
We found moderate to strong heritability for traits related to appetite such as eating too much, not eating enough and eating too fast. Univariate analysis estimates varied from 0.71 (95% CI: 0.49, 0.87) to 0.89 (0.75, 0.96) in younger children and from 0.44 (0.18, 0.66) to 0.56 (0.28, 0.78) in older children. Bivariate longitudinal analyses indicated modest to moderate genetic correlations across ages (r(A) varying from 0.34 to 0.58). Common genetic influences explained 17% to 43% of the phenotypic correlation between 2.5 and 9 years for these appetite-related behaviors. In 9-year-old children, food acceptance traits, such as refusing to eat and being fussy about food, had high heritability estimates, 0.84 (0.63, 0.94) and 0.85 (0.59, 0.96) respectively, while in younger children, the shared environment (i.e., common to both twins) contributed most to phenotypic variance. Variances in meal-pattern-related behaviors were mostly explained by shared environmental influences.
Genetic predispositions explain a large part of the variations in traits related to appetite during childhood, though our results suggest that as children get older, appetite-related behaviors become more sensitive to environmental influences outside the home. Still, for several traits environmental influences shared by twins appear to have the largest relative importance. This finding supports the notion that familial context has considerable potential to influence the development of healthy eating habits throughout childhood.
Cites: Behav Genet. 2004 Sep;34(5):503-1415319573
Cites: J Am Diet Assoc. 2005 Apr;105(4):541-815800554
BACKGROUND: Eating behavior may be implicated in the increasing prevalence of overweight and obesity, presumably in relation to easy access to energy-dense and highly palatable foods. OBJECTIVE: The aim of the present study was to disentangle genetic and environmental influences on eating behavior in a population-based cohort of male twins. DESIGN: The study included 326 dizygotic and 456 monozygotic male twin pairs aged 23-29 y from Sweden. The revised 21-item version of the Three-Factor Eating Questionnaire (TFEQ-R21) was used to assess eating behavior. This validated instrument consists of 3 dimensions: cognitive restraint, emotional eating, and uncontrolled eating. Structural equation modeling was used to estimate the heritability of eating behavior. RESULTS: Cognitive restraint was the only TFEQ-R21 scale that significantly correlated with BMI (r = 0.39, P
Dry matter intake (DMI) is a key component of feed efficiency in dairy cattle. In this study, we estimated genetic parameters of DMI over the first 24 lactation weeks in 3 dairy cattle breeds: Holstein, Nordic Red, and Jersey. In total, 1,656 primiparous cows (717 Holstein, 663 Nordic Red, and 276 Jersey) from Denmark, Finland, and Sweden were studied. For each breed, variance components, heritability, and repeatability for weekly DMI were estimated in 6 consecutive periods of the first 24 lactation weeks based on a repeatability animal model. Genetic correlations for DMI between different lactation periods were estimated using bivariate models. Based on our results, Holstein and Nordic Red cows had similar DMI at the beginning of lactation, but later in lactation Holstein cows had a slightly higher DMI than Nordic Red cows. In comparison, Jersey cows had a significantly lower DMI than the other 2 breeds within the first 24 lactation weeks. Heritability estimates for DMI ranged from 0.20 to 0.40 in Holsteins, 0.25 to 0.41 in Nordic Red, and 0.17 to 0.42 in Jerseys within the first 24 lactation weeks. Genetic and phenotypic variances for DMI varied along lactation within each breed and tended to be higher in the middle of lactation than at the beginning of the lactation. High genetic correlations were noted for DMI in lactation wk 5 to 24 in all 3 breeds, whereas DMI at early lactation (lactation wk 1 to 4) tended to be genetically different from DMI in the middle of lactation. The 3 breeds in this study might differ in their genetic variances for DMI, but the differences were not statistically significant in most of the studied periods. Breed differences for the genetic variance tended to be more obvious than for heritability. The potential breed differences in genetic variation for DMI should be considered in a future study using feed intake information from multiple breeds.
Feed conversion has been described as a "milk yield-tissue balance-appetite complex" in which energy inputs from feed intake and tissue balance impose a limit on milk yield. An experiment at the Agricultural University of Norway provided data to estimate genetic parameters of variables in this "complex." Fat-corrected milk yield, NE from roughage (NER) and BW were measured weekly on 353 first-lactation, dual-purpose Norwegian cows of 20 sires. Weekly weight change (WC) was computed from BW. Residual energy intake (RES) was calculated from energy balance (EB) corrected for WC. Amount of concentrate fed was adjusted according to stage of lactation and cows were randomly assigned to a normal or low level. Animals were given ad libitum access to grass silage. Data from the first and second trimesters of lactation were analyzed separately using an animal model containing fixed effects of 145 seasons in weeks, 24 subclasses of stages of lactation by levels of concentrate, and linear regression on age at calving and random effects of 512 animals and permanent environmental effects for the 353 animals with records. Cows fed at the low level of concentrate consumed more roughage and lost more weight but produced less milk. Catabolism of adipose tissue was poorly reflected by weight change. Heritability estimates for NER were .32 in the first trimester and .20 in the second; repeatability was .60. For EB, the respective estimates of heritability were .14 and .06, whereas repeatability was .55. No additive genetic variation was found for RES.
Obesity is frequently associated with eating disorders, and evidence indicates that both conditions are influenced by genetic factors. However, little is known about the genes influencing eating behaviors.
The objective was to identify genes associated with eating behaviors.
Three eating behaviors were assessed in 660 adults from the Quebec Family Study with the use of the Three-Factor Eating Questionnaire. A genome-wide scan was conducted with a total of 471 genetic markers spanning the 22 autosomes to identify quantitative trait loci for eating behaviors. Body composition and macronutrient and energy intakes were also measured.
Four quantitative trait loci were identified for disinhibition and susceptibility to hunger. Of these, the best evidence of linkage was found between a locus on chromosome 15q24-q25 and disinhibition (P 2 times that than in P73P homozygotes (3.6 compared with 1.5 kg; P
Intraventricular administration of glial cell line-derived neurotrophic factor (GDNF) in primate and humans to study Parkinson's disease (PD) has revealed the potential for GDNF to induce weight loss. Our previous data indicate that bilateral continuous hypothalamic GDNF overexpression via recombinant adeno-associated virus (rAAV) results in significant failure to gain weight in young rats and weight loss in aged rats. Based on these previous results, we hypothesized that because the nigrostriatal tract passes through the lateral hypothalamus, motor hyperactivity mediated by nigrostriatal dopamine (DA) may have been responsible for the previously observed effect on body weight. In this study, we compared bilateral injections of rAAV2/5-GDNF in hypothalamus versus substantia nigra (SN) in aged Brown-Norway X Fisher 344 rats. Nigrostriatal GDNF overexpression resulted in significantly greater weight loss than rats treated in hypothalamus. The nigral or hypothalamic GDNF-induced weight loss was unrelated to motor activity levels of the rats, though some of the weight loss could be attributed to a transient reduction in food intake. Forebrain DA levels did not account for the observed effects on body weight, although GDNF-induced increases in nucleus accumbens DA may have partially contributed to this effect in the hypothalamic GDNF-treated group. However, only nigrostriatal GDNF overexpression induced activation of phosphorylated extracellular signal-regulated kinase (p-ERK) in a small population of corticotrophin-releasing factor [corticotrophin-releasing hormone (CRH)] neurons located specifically in the medial parvocellullar division (MPD) of the paraventricular nucleus of the hypothalamus. Activation of these hypothalamic CRH neurons likely accounted for the observed metabolic effects leading to weight loss in obese rats.