Relation of the multilocus genetic composite reflecting high dopamine signaling capacity to future increases in BMI.

Because food intake exerts its rewarding effect by increasing dopamine (DA) signaling in reward circuitry, it theoretically follows that individuals with a greater number of genotypes putatively associated with high DA signaling capacity are at increased risk for overeating and subsequent weight gain. We tested the association between the multilocus genetic composite risk score, defined by the total number of genotypes putatively associated with greater DA signaling capacity (i.e. TaqIA A2 allele, DRD2-141C Ins/Del and Del/Del genotypes, DRD4-S allele, DAT1-S allele, and COMT Val/Val genotype), and future increases in Body Mass Index (BMI) in three prospective studies. Participants in Study 1 (N = 30; M age = 15.2; M baseline BMI = 26.9), Study 2 (N = 34; M age = 20.9; M baseline BMI = 28.2), and Study 3 (N = 162; M age = 15.3, M baseline BMI = 20.8) provided saliva samples from which epithelial cells were collected, permitting DNA extraction. The multilocus genetic composite risk score was associated with future increases in BMI in all three studies (Study 1, r = 0.37; Study 2, r = 0.22; Study 3, r = 0.14) and the overall sample (r = 0.19). DRD4-S was associated with increases in BMI in Study 1 (r = 0.42), Study 2 (r = 0.27), and in the overall sample (r = 0.17). DAT1-S was associated with increases in BMI in Study 3 (r = 0.17) and in the overall sample (r = 0.12). There were no associations between the other genotypes (TaqIA, COMT, and DRD2-141C) and change in BMI over 2-year follow-up. Data suggest that individuals with a genetic propensity for greater DA signaling capacity are at risk for future weight gain and that combining alleles that theoretically have a similar function may provide a more reliable method of modeling genetic risk associated with future weight gain than individual genotypes.

Genetic parameters for mouth size and their influence on growth traits in pasture-raised Nelore cattle.

Evaluating traits that allow breeders to increase production efficiency in beef production systems is important. The mouth size (MS) score is a trait easily measured and implemented by breeders. Bite size is related to MS in beef cattle and is a determinant of daily feed intake of pasture-raised animals, influencing their growth. The aim of this study was to estimate genetic parameters for MS, weaning weight (WW) and postweaning weight gain (PWG) of Nelore cattle and to evaluate the influence of the interaction between MS and WW on PWG. Phenotypic records of 134,282 Nelore animals born between 1995 and 2019 were used. Variance components were estimated using multitrait animal model with the Bayesian method. The model included the contemporary group as fixed effect, age at measurement of the trait as linear covariate, and direct additive genetic and residual effects as random effects. For WW, random maternal and maternal permanent environmental effects were added to the model. A Bayesian approach was used to analyze the interaction between WW clusters and MS. The heritability estimates were 0.24, 0.15, and 0.23 for MS, WW, and PWG, respectively. The genetic correlation between variables studied ranged from 0.24 to 0.46. The results suggest that animals with a larger mouth tend to have greater PWG, demonstrating the positive influence of MS score on the postweaning performance of cattle. The direct heritability estimates confirm the possibility of selecting animals for the traits studied.

Evaluating traits that allow breeders to increase production efficiency in beef production systems is important. The mouth size (MS) score is a trait easily measured and implemented by breeders. Our results showed that MS in Nelore cattle is a heritable trait, and it is favorably associated with growth traits, indicating that animals with larger mouth are heavier at weaning and gain more weight after weaning on pasture. MS score should be further explored to evaluate its complexity and inclusion in breeding programs incorporating data collected from cattle raised under pasture conditions.

Reward circuitry responsivity to food predicts future increases in body mass: moderating effects of DRD2 and DRD4.

OBJECTIVE: To determine whether responsivity of reward circuitry to food predicts future increases in body mass and whether polymorphisms in DRD2 and DRD4 moderate these relations. DESIGN: The functional magnetic resonance imaging (fMRI) paradigm investigated blood oxygen level dependent activation in response to imagined intake of palatable foods, unpalatable foods, and glasses of water shown in pictures. DNA was extracted from saliva samples using standard salting-out and solvent precipitation methods. PARTICIPANTS: Forty-four adolescent female high school students ranging from lean to obese. MAIN OUTCOME: Future increases in body mass index (BMI). RESULTS: Weaker activation of the frontal operculum, lateral orbitofrontal cortex, and striatum in response to imagined intake of palatable foods, versus imagined intake of unpalatable foods or water, predicted future increases in body mass for those with the DRD2 TaqIA A1 allele or the DRD4-7R allele. Data also suggest that for those lacking these alleles, greater responsivity of these food reward regions predicted future increases in body mass. DISCUSSION: This novel prospective fMRI study indicates that responsivity of reward circuitry to food increases risk for future weight gain, but that genes that impact dopamine signaling capacity moderate the predictive effects, suggesting two qualitatively distinct pathways to unhealthy weight gain based on genetic risk.

PLGA microsphere-mediated growth hormone release hormone expression induces intergenerational growth.

To improve animal growth, growth hormone-releasing hormone (GHRH) expression vectors that maintain constant GHRH expression can be directly injected into muscles. To deliver the GHRH expression vectors, biodegradable microspheres have been used as a sustained release system. Although administering GHRH through microspheres is a common practice, the intergenerational effects of this delivery system are unknown. To investigate the intergenerational effects of polylactic-co-glycolic acid (PLGA) encapsulated plasmid-mediated GHRH supplements, pCMV-Rep-GHRH microspheres were injected into pregnant mice. Growth and expression of GHRH were measured in the offspring. RT-PCR and immunohistochemistry reveal GHRH expression 3-21 days post-injection. The proportion of GH-positive cells in the GHRH treated offspring was 48.2% higher than in the control group (P < 0.01). The GHRH treated offspring were 6.15% (P < 0.05) larger than the control offspring. At day 49 post-injection, IGF-I serum levels were significantly higher in the treatment group than in the control group. This study confirms that intramuscular expression of GHRH mediated by PLGA microspheres significantly enhances intergenerational growth.