Characterization of metabolic phenotypes and distinctive genes in mice with low-weight gain.

Being overweight exacerbates various metabolic diseases, necessitating the identification of target molecules for obesity control. In the current study, we investigated common physiological features related to metabolism in mice with low weight gain: (1) G protein-coupled receptor, family C, group 5, member B-knockout; (2) gastric inhibitory polypeptide receptor-knockout; and (3) Iroquois-related homeobox 3-knockout. Moreover, we explored genes involved in metabolism by analyzing differentially expressed genes (DEGs) between low-weight gain mice and the respective wild-type control mice. The common characteristics of the low-weight gain mice were low inguinal white adipose tissue (iWAT) and liver weight despite similar food intake along with lower blood leptin levels and high energy expenditure. The DEGs of iWAT, epididymal (gonadal) WAT, brown adipose tissue, muscle, liver, hypothalamus, and hippocampus common to these low-weight gain mice were designated as candidate genes associated with metabolism. One such gene tetraspanin 7 (Tspan7) from the iWAT was validated using knockout and overexpressing mouse models. Mice with low Tspan7 expression gained more weight, while those with high Tspan7 expression gained less weight, confirming the involvement of the Tspan7 gene in weight regulation. Collectively, these findings suggest that the candidate gene list generated in this study contains potential target molecules for obesity regulation. Further validation and additional data from low-weight gain mice will aid in understanding the molecular mechanisms associated with obesity.

Pharmacogenetics of weight gain following switch from efavirenz- to integrase inhibitor-containing regimens.

BACKGROUND: Excessive weight gain affects some persons with HIV after switching to integrase strand transfer inhibitor (INSTI)-containing antiretroviral therapy (ART). We studied associations between CYP2B6 genotype and weight gain after ART switch among ACTG A5001 and A5322 participants. METHODS: Eligible participants switched from efavirenz- to INSTI-containing ART, had genotype data, and had weight data at least once from 4 weeks to 2 years post-switch. Multivariable linear mixed effects models adjusted for race/ethnicity, CD4, age, BMI and INSTI type assessed relationships between CYP2B6 genotype and estimated differences in weight change. RESULTS: A total of 159 eligible participants switched ART from 2007 to 2019, of whom 138 had plasma HIV-1 RNA < 200 copies/mL (65 CYP2B6 normal, 56 intermediate, 17 poor metabolizers). Among participants with switch HIV-1 RNA < 200 copies/mL, weight increased in all 3 CYP2B6 groups. The rate of weight gain was greater in CYP2B6 poor than in CYP2B6 normal metabolizers overall, and within 9 subgroups (male, female, White, Black, Hispanic, dolutegravir, elvitegravir, raltegravir, and TDF in the pre-switch regimen); only in Hispanic and elvitegravir subgroups were these associations statistically significant ( P  < 0.05). Compared to normal metabolizers, CYP2B6 intermediate status was not consistently associated with weight gain. CONCLUSION: CYP2B6 poor metabolizer genotype was associated with greater weight gain after switch from efavirenz- to INSTI-containing ART, but results were inconsistent. Weight gain in this setting is likely complex and multifactorial.

Identification of four novel loci associated with psychotropic drug-induced weight gain in a Swiss psychiatric longitudinal study: A GWAS analysis.

Patients suffering from mental disorders are at high risk of developing cardiovascular diseases, leading to a reduction in life expectancy. Genetic variants can display greater influence on cardiometabolic features in psychiatric cohorts compared to the general population. The difference is possibly due to an intricate interaction between the mental disorder or the medications used to treat it and metabolic regulations. Previous genome wide association studies (GWAS) on antipsychotic-induced weight gain included a low number of participants and/or were restricted to patients taking one specific antipsychotic. We conducted a GWAS of the evolution of body mass index (BMI) during early (i.e., ≤ 6) months of treatment with psychotropic medications inducing metabolic disturbances (i.e., antipsychotics, mood stabilizers and some antidepressants) in 1135 patients from the PsyMetab cohort. Six highly correlated BMI phenotypes (i.e., BMI change and BMI slope after distinct durations of psychotropic treatment) were considered in the analyses. Our results showed that four novel loci were associated with altered BMI upon treatment at genome-wide significance (p < 5 × 10-8): rs7736552 (near MAN2A1), rs11074029 (in SLCO3A1), rs117496040 (near DEFB1) and rs7647863 (in IQSEC1). Associations between the four loci and alternative BMI-change phenotypes showed consistent effects. Replication analyses in 1622 UK Biobank participants under psychotropic treatment showed a consistent association between rs7736552 and BMI slope (p = 0.017). These findings provide new insights into metabolic side effects induced by psychotropic drugs and underline the need for future studies to replicate these associations in larger cohorts.

Genomic analysis of feed efficiency traits in beef cattle using random regression models.

Feed efficiency plays a major role in the overall profitability and sustainability of the beef cattle industry, as it is directly related to the reduction of the animal demand for input and methane emissions. Traditionally, the average daily feed intake and weight gain are used to calculate feed efficiency traits. However, feed efficiency traits can be analysed longitudinally using random regression models (RRMs), which allow fitting random genetic and environmental effects over time by considering the covariance pattern between the daily records. Therefore, the objectives of this study were to: (1) propose genomic evaluations for dry matter intake (DMI), body weight gain (BWG), residual feed intake (RFI) and residual weight gain (RWG) data collected during an 84-day feedlot test period via RRMs; (2) compare the goodness-of-fit of RRM using Legendre polynomials (LP) and B-spline functions; (3) evaluate the genetic parameters behaviour for feed efficiency traits and their implication for new selection strategies. The datasets were provided by the EMBRAPA-GENEPLUS beef cattle breeding program and included 2920 records for DMI, 2696 records for BWG and 4675 genotyped animals. Genetic parameters and genomic breeding values (GEBVs) were estimated by RRMs under ssGBLUP for Nellore cattle using orthogonal LPs and B-spline. Models were compared based on the deviance information criterion (DIC). The ranking of the average GEBV of each test week and the overall GEBV average were compared by the percentage of individuals in common and the Spearman correlation coefficient (top 1%, 5%, 10% and 100%). The highest goodness-of-fit was obtained with linear B-Spline function considering heterogeneous residual variance. The heritability estimates across the test period for DMI, BWG, RFI and RWG ranged from 0.06 to 0.21, 0.11 to 0.30, 0.03 to 0.26 and 0.07 to 0.27, respectively. DMI and RFI presented within-trait genetic correlations ranging from low to high magnitude across different performance test-day. In contrast, BWG and RWG presented negative genetic correlations between the first 3 weeks and the other days of performance tests. DMI and RFI presented a high-ranking similarity between the GEBV average of week eight and the overall GEBV average, with Spearman correlations and percentages of individuals selected in common ranging from 0.95 to 1.00 and 93 to 100, respectively. Week 11 presented the highest Spearman correlations (ranging from 0.94 to 0.98) and percentages of individuals selected in common (ranging from 85 to 94) of BWG and RWG with the average GEBV of the entire period of the test. In conclusion, the RRM using linear B-splines is a feasible alternative for the genomic evaluation of feed efficiency. Heritability estimates of DMI, RFI, BWG and RWG indicate enough additive genetic variance to achieve a moderate response to selection. A new selection strategy can be adopted by reducing the performance test to 56 days for DMI and RFI selection and 77 days for BWG and RWG selection.

Genetic parameters, genetic trends and correlated responses of growth traits considering maternal ability in Nelore cattle.

The growth of Nelore cattle was analysed considering the following performance parameters; the effect of the calving order of cows on the phenotypic expression of birth weight (BW), average daily gain from birth to weaning (BWG), and weaning weight (WW), the estimated genetic parameters for the traits, including the covariance components between direct and maternal genetic effects. Genetic trends and correlated responses were also obtained for the studied traits. The calving order of cows, as well as other fixed effects used to obtain the adjusted phenotypic means, were statistically significant (p < 0.001) for studied traits. Direct heritability was estimated at 0.24 ± 0.01 (BW), 0.15 ± 0.01 (BWG), and 0.18 ± 0.01 (WW), while maternal heritability was 0.06 ± 0.01 (BW), 0.12 ± 0.01 (BWG), and 0.11 ± 0.01 (WW). The correlations between direct and maternal effects within the same trait were negligible. Moderate to higher direct genetic correlations (ranging from 0.54 ± 0.04 to 0.98 ± 0.01) and maternal genetic correlations (ranging from 0.34 ± 0.09 to 0.99 ± 0.002) were estimated between the studied traits. Unlike direct genetic effects, there was no significant change in maternal genetic effects over time (p > 0.05). These results indicated the need for revising selection indexes for enhancing maternal ability. Correlated responses were generally lower compared to direct responses, except for BWG. The selection for BWG, considering the maternal genetic effect, would be more efficient to improve maternal ability of the cows for pre-weaning growth in relation to selection for WW. Our results found that direct genetic merit improves pre-weaning weight and this trait can be incorporated into the breeding goal as reflected in the WW.

Obesity-Related Single-Nucleotide Polymorphisms and Weight Gain Following First-Line Antiretroviral Therapy.

BACKGROUND: We studied the association of obesity-related single-nucleotide polymorphisms (OR-SNPs) with weight gain after antiretroviral therapy (ART) in people with human immunodeficiency virus (HIV; PWH). METHODS: Participants were ART-naive PWH from the Spanish HIV Research Cohort who started ART from 2014 onward and had blood/DNA deposited in the cohort Biobank. The primary outcome was change in weight at 96 weeks after starting ART. We genotyped 14 OR-SNPs from a meta-analysis of genome-wide association studies of body mass index (BMI) loci. Changes over time in weight and BMI were studied using adjusted linear mixed models. RESULTS: A total of 1021 PWH were included. The mean weight gain over 96 weeks was 2.90 (95% confidence interval, 2.54-3.26) kg. Factors associated with higher weight gain were female sex, birth in sub-Saharan Africa, prior AIDS, CD4+ <200 cells/µL, HIV-RNA >100 000 copies/mL, negative hepatitis C virus serology, and use of tenofovir alafenamide. A significant association was found between ZC3H4 rs3810291 GG genotype and BCDIN3D/FAIM2 rs7138803 GG genotype polymorphisms and weight and BMI increase. The estimated adjusted mean (standard error [SE]) of weight gain was 4.26 (0.56) kg in ZC3H4 rs3810291 GG carriers and 2.66 (0.19) kg in AA/AG carriers (P = .007). Likewise the estimated weight gain at 96 weeks was 3.35 (0.29) kg in BCDIN3D/FAIM2 rs7138803 GG carriers and 2.51 (0.24) kg in AG/AA carriers (P = .020). CONCLUSIONS: Genetic factors may play a role in weight gain after ART initiation. Further work is needed to replicate our findings and understand how the identified SNPs lead to higher weight gain in this context.

Associations of height, body mass index, and weight gain with breast cancer risk in carriers of a pathogenic variant in BRCA1 or BRCA2: the BRCA1 and BRCA2 Cohort Consortium.

INTRODUCTION: Height, body mass index (BMI), and weight gain are associated with breast cancer risk in the general population. It is unclear whether these associations also exist for carriers of pathogenic variants in the BRCA1 or BRCA2 genes. PATIENTS AND METHODS: An international pooled cohort of 8091 BRCA1/2 variant carriers was used for retrospective and prospective analyses separately for premenopausal and postmenopausal women. Cox regression was used to estimate breast cancer risk associations with height, BMI, and weight change. RESULTS: In the retrospective analysis, taller height was associated with risk of premenopausal breast cancer for BRCA2 variant carriers (HR 1.20 per 10 cm increase, 95% CI 1.04-1.38). Higher young-adult BMI was associated with lower premenopausal breast cancer risk for both BRCA1 (HR 0.75 per 5 kg/m2, 95% CI 0.66-0.84) and BRCA2 (HR 0.76, 95% CI 0.65-0.89) variant carriers in the retrospective analysis, with consistent, though not statistically significant, findings from the prospective analysis. In the prospective analysis, higher BMI and adult weight gain were associated with higher postmenopausal breast cancer risk for BRCA1 carriers (HR 1.20 per 5 kg/m2, 95% CI 1.02-1.42; and HR 1.10 per 5 kg weight gain, 95% CI 1.01-1.19, respectively). CONCLUSION: Anthropometric measures are associated with breast cancer risk for BRCA1 and BRCA2 variant carriers, with relative risk estimates that are generally consistent with those for women from the general population.

Preventing high-fat diet-induced obesity and related metabolic disorders by hydrodynamic transfer of Il-27 gene.

BACKGROUND AND OBJECTIVES: Interleukin-27 (IL-27) is a multifaceted heterodimer cytokine that exerts both pro-inflammatory and anti-inflammatory effects under different physiological conditions. IL-27 signaling plays a role in promoting energy expenditure through enhanced thermogenesis. The objective of the study is to determine the functional role of IL-27 in regulating weight gain, and glucose and lipid homeostasis in mice fed a high-fat diet (HFD). METHODS: C57BL/6 mice were hydrodynamically transferred with pLIVE-IL-27 plasmids to achieve elevated level of IL-27 in blood and then kept on a HFD for 8 weeks. The impacts of Il-27 gene transfer on HFD-induced weight gain, adiposity, hepatic lipid accumulation, insulin resistance, glucose homeostasis and the mRNA levels of genes responsible for lipogenesis, glucose homeostasis and proinflammation were assessed by methods of biochemistry, histology, and molecular biology. RESULTS: Hydrodynamic gene transfer of Il-27 gene resulted in a peak level of serum IL-27 in mice at 14.5 ng/ml 24 h after gene transfer followed by a sustained level at 2 ng/ml. The elevated level of IL-27 blocked HFD-induced fat accumulation and weight gain without reducing food intake. It also prevented metabolic abnormities of liver steatosis and insulin resistance. IL-27 overexpression promoted expression of major thermogenic genes in brown adipose tissues; and attenuated chronic inflammation and macrophage infiltration into white adipose tissues. CONCLUSIONS: The results demonstrate that regulation of IL-27 level could be an effective strategy for management of obesity and obesity-related metabolic diseases.

Polygenic risk scores analyses of psychiatric and metabolic traits with antipsychotic-induced weight gain in schizophrenia: an exploratory study.

Given the polygenic nature of antipsychotic-induced weight gain (AIWG), we investigated whether polygenic risk scores (PRS) for various psychiatric and metabolic traits were associated with AIWG. We included individuals with schizophrenia (SCZ) of European ancestry from two cohorts (N = 151, age = 40.3 ± 11.8 and N = 138, age = 36.5 ± 10.8). We investigated associations of AIWG defined as binary and continuous variables with PRS calculated from genome-wide association studies of body mass index (BMI), coronary artery disease (CAD), fasting glucose, fasting insulin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, type 1 and 2 diabetes mellitus, and SCZ, using regression models. We observed nominal associations (uncorrected p < 0.05) between PRSs for BMI, CAD, and LDL-C, type 1 diabetes, and SCZ with AIWG. While results became non-significant after correction for multiple testing, these preliminary results suggest that PRS analyses might contribute to identifying risk factors of AIWG and might help to elucidate mechanisms at play in AIWG.

The heritability of weight gain in infancy: A population-based twin study.

BACKGROUND: Rapid weight gain during infancy is a strong predictor of childhood obesity and is affected by genetic and environmental factors. Identifying ages with low heritability will allow for targeted interventions that might be able to prevent the adverse effects of childhood obesity. OBJECTIVES: The objective of the study is to estimate the heritability of weight gain from birth to defined ages during infancy, as well as during 6-month periods from birth to 18 months of age. We address this by leveraging large-scale computerised anthropometric data from the state-run network of well-baby clinics in Israel. METHODS: We performed a population-based twin study. We extracted weight measurements recorded between birth to 24 months from well-baby clinics for 9388 twin pairs born in Israel between 2011 and 2015. The reported sexes of the twins were used as a proxy for their zygosity status. We estimated the heritability of the weight z-score change from birth to specific ages and during particular periods in infancy. To assess the validity of the results, we repeated the analysis in a sub-cohort of twin pairs with complete weight measurements. RESULTS: During the first 2 years of life, heritability was lowest for birthweight ( h 2 = 0.40 ± 0.11 ). Heritability for weight gain since birth was highest at 4 months ( h 2 = 0.87 ± 0.13 ), and then gradually decreased until age 18 months ( h 2 = 0.62 ± 0.13 ). Estimating the heritability in 6-month intervals from birth to 18 months, heritability was highest during the 6-12-month interval ( h 2 = 0.84 ± 0.14 ), and was substantially lower during the subsequent 12-18-month interval ( h 2 = 0.43 ± 0.16 ). CONCLUSIONS: Heritability of weight gain decreases substantially in the second year of life, suggesting that this period could be an appropriate time for interventions for infants who are at an increased risk of childhood obesity.

Disentangling the dynamics of energy allocation to develop a proxy for robustness of fattening pigs.

BACKGROUND: There is a growing need to improve robustness of fattening pigs, but this trait is difficult to phenotype. Our first objective was to develop a proxy for robustness of fattening pigs by modelling the longitudinal energy allocation coefficient to growth, with the resulting environmental variance of this allocation coefficient considered as a proxy for robustness. The second objective was to estimate its genetic parameters and correlations with traits under selection and with phenotypes that are routinely collected. In total, 5848 pigs from a Pietrain NN paternal line were tested at the AXIOM boar testing station (Azay-sur-Indre, France) from 2015 to 2022. This farm is equipped with an automatic feeding system that records individual weight and feed intake at each visit. We used a dynamic linear regression model to characterize the evolution of the allocation coefficient between the available cumulative net energy, which was estimated from feed intake, and cumulative weight gain during the fattening period. Longitudinal energy allocation coefficients were analysed using a two-step approach to estimate both the genetic variance of the coefficients and the genetic variance in their residual variance, which will be referred to as the log-transformed squared residual (LSR). RESULTS: The LSR trait, which could be interpreted as an indicator of the response of the animal to perturbations/stress, showed a low heritability (0.05 ± 0.01), a high favourable genetic correlation with average daily growth (- 0.71 ± 0.06), and unfavourable genetic correlations with feed conversion ratio (- 0.76 ± 0.06) and residual feed intake (- 0.83 ± 0.06). Segmentation of the population in four classes using estimated breeding values for LSR showed that animals with the lowest estimated breeding values were those with the worst values for phenotypic proxies of robustness, which were assessed using records routinely collected on farm. CONCLUSIONS: Results of this study show that selection for robustness, based on estimated breeding values for environmental variance of the allocation coefficients to growth, can be considered in breeding programs for fattening pigs.

The relationships between specific dynamic action, nutrient retention and feed conversion ratio in farmed freshwater Chinook salmon (Oncorhynchus tshawytscha).

Improving the feed conversion ratio (FCR; the amount of feed consumed relative to the amount of weight gain) can reduce both production costs and environmental impacts of farmed fish. The aim of this study was to investigate what drives FCR to understand how nutrients are retained, as well as the amount of oxygen consumed for digestion, absorption and assimilation (a metabolic process known as specific dynamic action, SDA). Feed-efficient and inefficient Chinook salmon (Oncorhynchus tshawytscha) in fresh water were identified using ballotini beads and X-radiography that tracked individual feed intake across three assessment periods under satiated feeding. This allowed a comparison of physiological traits and body composition between the two FCR phenotypes over two time points as Chinook salmon grew from 305 to 620 g. Fish with higher daily feed intake (DFI) had higher daily weight gain (DWG) as expected. Nonetheless, the relationship between FCR and DFI as well as FCR and DWG was variable between time points. FCR and DWG were not correlated at the first time point and were negatively correlated at the second time point. In contrast, FCR and DFI were positively correlated at the first time point but not the second. Despite this, efficient fish ate smaller meals and retained more protein, lipid and energy in their body tissues. There was no detectable difference in metabolism between the two FCR phenotypes with respect to minimal resting metabolic rate, maximum metabolic rate, aerobic scope, or SDA parameters. In conclusion, FCR is not consistently associated with growth and metabolic differences in freshwater Chinook salmon, but FCR-efficient fish retain more nutrients and consume smaller meals.

Growth rate and efficiency-related traits in Kermani lambs: estimations of (co)variance components and genetic parameters.

Using Kermani sheep, the current study estimated (co)variance components and genetic parameters for average daily gain, Kleiber's ratio, growth efficiency, and relative growth rate. Data were analyzed by the average information restricted maximum likelihood (AI-REML) method using six animal models with different combinations of direct and maternal effects. The best-fitting model was determined after testing for improvement in log-likelihood values. The estimates of h2 for average daily gain (ADG), Klieber's ratio (KR), growth efficiency (GE), and relative growth rate (RGR) in pre- and post-weaning phases were 0.13 ± 0.6 and 0.17 ± 0.02, 0.12 ± 0.04, and 0.16 ± 0.03; 0.05 ± 0.05 and 0.07 ± 0.03 and 0.06 ± 0.02 and 0.07 ± 0.01, respectively. Maternal heritabilities (m2) ranged from 0.03 ± 0.01 for relative growth rate in pre-weaning phase to 0.11 ± 0.04 for average daily gain in post-weaning period. The maternal permanent environmental component (Pe2) accounted for 3 to 13% to the phenotypic variance for all the studied traits. Estimated values of additive coefficient of variations (CVA) ranged from 2.79% for relative growth rate at 6 months of age to 23.74% for growth efficiency at yearling age. Genetic and phenotypic correlations among traits were ranged from -0.687 to 0.946 and -0.648 to 0.918, respectively. The result indicated that selection for growth rate and efficiency-related traits would also be less effective in achieving genetic change, because there was little additive genetic variation among Kermani lambs.

Heritability and environmental influence on pre-weaning traits in Kilis goats.

Birth and weaning weights, average daily weight gain, and Kleiber ratio are important indicator traits in selection decision. The phenotypic expression of these traits is determined by the genetic background, environmental effects, and their interactions. The objective of this study was to estimate genetic parameters regarding birth (BW) and weaning weights (WW) and average daily weight gain (ADWG), Kleiber ratio (KR), and obtain the effects of sex, birth type, herd, and year. The data consisted of 2274 Kilis goats with pedigree information obtained from 53 bucks and 774 does in 4 generations. The restricted maximum likelihood (REML) procedure was conducted with an animal linear mixed model. Sex, birth type, herd, and year were found to be statistically significant (p value < 0.001) for all traits. Moderate direct heritabilities (ha2) for BW, WW, ADW, and KR were found to be as 0.18 ± 0.03, 0.50 ± 0.04, 0.47 ± 0.04, and 0.37 ± 0.05, respectively. The proportion of maternal permanent environmental effect (c2) to the total phenotypic variance (σ2p) was estimated as 0.00 ± 0.00, 0.12 ± 0.02, 0.11 ± 0.02, and 0.18 ± 0.03 for BW, WW, ADWG, and KR, respectively. The genetic, phenotypic, and environmental correlations between the pre-weaning growth traits were found to be ranging from - 0.02 to 0.99. Thus, our study suggests moderate heritabilities and positive and relatively high genetic correlations among the observed pre-weaning growth traits. These results have implications in terms of providing rapid genetic progress for these traits in breeding programs of Kilis goats.

Genetic evaluation of growth rate and efficiency-related traits in Dorper × local crossbred sheep population.

The present study was carried out to estimate genetic and phenotypic parameters for growth rate and efficiency-related traits in Dorper crossbred sheep population. Data on body weight collected from 2012 to 2021 at Debre Birhan Agricultural Research Center, Amhara Regional State, Ethiopia, were used to estimate phenotypic and genetic parameters for daily gain from birth to weaning (DG0-3), daily gain from weaning to 6 months (DG3-6), and daily gain from 6 months to yearling (DG6-12) and corresponding Kleiber ratios (KR0-3, KR3-6, KR6-12), efficiency of growth (GE0-3, GE3-6, GE6-12), and relative growth rate (RG0-3, RG3-6, RG6-12). Genetic parameters were estimated by restricted maximum likelihood (REML) procedure fitting six different univariate animal models and the most appropriate model for each trait was determined by log-likelihood ratio test. Multivariate analysis was carried out to estimate correlations between traits. Year and season of birth had a significant effect (p<0.001) in all studied traits. Direct heritability estimates for DG0-3, DG3-6, DG6-12, KR0-3, KR3-6, KR6-12, GE0-3, GE3-6, GE6-12, GR0-3, GR3-6, and GR6-12 were 0.45±0.15, 0.04±0.06, 0.15±0.11, 0.30±0.08, 0.13±0.11, 0.14±0.12, 0.34±0.15, 0.39±0.17, 0.31±0.14, 0.25±0.08, 0.23±0.13, and 0.23±0.13 respectively. Genetic correlation estimates between DG3-6 and other traits were positive and high in magnitude to their respective growth phase (0.95, 0.86, and 0.91 for KR3-6, GE3-6, and GR3-6 respectively). As the Dorper crossbred sheep are reaches market weight at about 6 months of age, focusing on improving traits measured during weaning to 6 months of age is more feasible. Selection based on DG3-6 is recommended to improve efficiency-related traits.

Estimates of genetic parameters and genetic trend for growth traits and Kleiber ratio of Holstein-Friesian calves.

Growth traits of calves, which are quantitative characteristics determining cattle business profitability, vary according to genetic and environmental factors. In other words, growth traits depend on the genetics of the individual and vary with farm management. The aim of this study was to investigate the effective environmental factors, genetic parameters, and genetic trends for some growth traits and the Kleiber ratio (KR) in Holstein-Friesian calves. For this purpose, the records of 724 calves, progeny of 566 dams and 29 sires, reared between 2017 and 2019 on a private dairy farm in Türkiye, were used. MTDFREML software was utilized to estimate genetic parameters and genetic trends of growth traits and KR. In this study, regarding weight, the mean of birth weight (BW), 60-day weight (W60), and 90-day weight (W90) were 39.76 ± 6.15 kg, 69.23 ± 10.93 kg, and 95.76 ± 16.48 kg, respectively. Concerning weight gain, 1-60 daily weight gain (DWG1-60), 60-90 daily weight gain (DWG60-90), and 1-90 daily weight gain (DWG1-90) were 0.49 ± 0.16 kg, 0.91 ± 0.34 kg, and 0.63 ± 0.17 kg, respectively. With respect to KR, 1-60 daily KR (KR1-60), 60-90 daily KR (KR60-90), and 1-90 daily KR (KR1-90) were 2.03 ± 0.48, 2.93 ± 0.89, and 2.02 ± 0.34, respectively. As a result of the GLM analysis, only the effect of the birth season on all traits was significant (p < 0.05 or p < 0.01). In addition, it was detected that sex had a significant effect on BW and W60 (p < 0.05 or p < 0.01). For all traits, only the effect of parity on KR1-60 was not significant. In REML analysis, direct heritability differed between 0.26 ± 0.16 and 0.81 ± 0.27 obtained at DWG1-90 and DWG1-60, respectively. Also, the highest repeatability (0.100) was obtained in DWG1-60. It was detected that mass selection could be used in all traits for breeding program. In BLUP analysis, the current population had an increasing trend for BW and W90 and a decreasing trend for W60. However, there was no significant change in other weight gain traits and KR over the years. Calves with high breeding values for BW, W60, W90, DWG1-60, DWG60-90, and DWG1-90 should be chosen for selection programs. But for KR1-60, KR60-90, and KR1-90, calves with low breeding values should be selected for efficiency. Also, KR evaluated would contribute to the literature and other research should be studied regarding KR.

Genetic association between feed efficiency, growth, scrotal circumference, and carcass traits in Guzerat cattle.

The objective of this study was to estimate the genetic parameters for feed efficiency-related traits and their genetic correlations with growth, male fertility, and carcass traits using multi-trait analysis in Guzerat cattle. Further, it aimed to predict the direct and correlated responses for feed efficiency traits when selection was applied for growth, male fertility, and carcass traits. The evaluated traits were adjusted weight at 120 (W120), 210 (W210), 365 (W365), and 450 days of age (W450), adjusted scrotal circumference at 365 days of age (SC365) and at 450 days of age (SC450), scrotal circumference, ribeye area (REA), backfat thickness (BFT), rump fat thickness (RFT), residual feed intake (RFI), and dry matter intake (DMI). The genetic parameters were obtained by the restricted maximum likelihood method (REML), using an animal model in multi-trait analyses. The heritability estimates for W120, W210, W365, W450, SC365, and SC450 varied from low to high (0.17 to 0.39). The carcass traits, REA, BFT, and RFT, displayed low to moderate heritability estimates, 0.27, 0.10, and 0.31, respectively. The heritability estimates for RFI (0.15) and DMI (0.23) were low and moderate, respectively. The RFI showed low genetic correlations with growth traits, ranging from - 0.07 to 0.22, from 0.03 to 0.05 for scrotal circumference, and from - 0.35 to 0.16 for carcass, except for DMI, which ranged from 0.42 to 0.46. The RFI and DMI presented enough additive genetic variability to be used as selection criteria in Guzerat breed genetic improvement program. Additionally, the response to selection for RFI would be higher when selection is performed directly for this trait. The selection for residual feed intake would not promote unfavorable correlated responses for scrotal circumference, carcass (yield and finish), and growth traits. Therefore, the selection for more efficient animals would not compromise the productive, reproductive, and carcass performance, contributing to reduce the production costs, increasing the profitability and sustainability of beef cattle production in tropical areas.

Large-scale association study on daily weight gain in pigs reveals overlap of genetic factors for growth in humans.

BACKGROUND: Imputation from genotyping array to whole-genome sequence variants using resequencing of representative reference populations enhances our ability to map genetic factors affecting complex phenotypes in livestock species. The accumulation of knowledge about gene function in human and laboratory animals can provide substantial advantage for genomic research in livestock species. RESULTS: In this study, 201,388 pigs from three commercial Danish breeds genotyped with low to medium (8.5k to 70k) SNP arrays were imputed to whole genome sequence variants using a two-step approach. Both imputation steps achieved high accuracies, and in total this yielded 26,447,434 markers on 18 autosomes. The average estimated imputation accuracy of markers with minor allele frequency ≥ 0.05 was 0.94. To overcome the memory consumption of running genome-wide association study (GWAS) for each breed, we performed within-breed subpopulation GWAS then within-breed meta-analysis for average daily weight gain (ADG), followed by a multi-breed meta-analysis of GWAS summary statistics. We identified 15 quantitative trait loci (QTL). Our post-GWAS analysis strategy to prioritize of candidate genes including information like gene ontology, mammalian phenotype database, differential expression gene analysis of high and low feed efficiency pig and human GWAS catalog for height, obesity, and body mass index, we proposed MRAP2, LEPROT, PMAIP1, ENSSSCG00000036234, BMP2, ELFN1, LIG4 and FAM155A as the candidate genes with biological support for ADG in pigs. CONCLUSION: Our post-GWAS analysis strategy helped to identify candidate genes not just by distance to the lead SNP but also by multiple sources of biological evidence. Besides, the identified QTL overlap with genes which are known for their association with human growth-related traits. The GWAS with this large data set showed the power to map the genetic factors associated with ADG in pigs and have added to our understanding of the genetics of growth across mammalian species.

Susceptibility to diet-induced obesity at thermoneutral conditions is independent of UCP1.

Activation of uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) upon cold stimulation leads to substantial increase in energy expenditure to defend body temperature. Increases in energy expenditure after a high-caloric food intake, termed diet-induced thermogenesis, are also attributed to BAT. These properties render BAT a potential target to combat diet-induced obesity. However, studies investigating the role of UCP1 to protect against diet-induced obesity are controversial and rely on the phenotyping of a single constitutive UCP1-knockout model. To address this issue, we generated a novel UCP1-knockout model by Cre-mediated deletion of exon 2 in the UCP1 gene. We studied the effect of constitutive UCP1 knockout on metabolism and the development of diet-induced obesity. UCP1 knockout and wild-type mice were housed at 30°C and fed a control diet for 4 wk followed by 8 wk of high-fat diet. Body weight and food intake were monitored continuously over the course of the study, and indirect calorimetry was used to determine energy expenditure during both feeding periods. Based on Western blot analysis, thermal imaging and noradrenaline test, we confirmed the lack of functional UCP1 in knockout mice. However, body weight gain, food intake, and energy expenditure were not affected by loss of UCP1 function during both feeding periods. We introduce a novel UCP1-KO mouse enabling the generation of conditional UCP1-knockout mice to scrutinize the contribution of UCP1 to energy metabolism in different cell types or life stages. Our results demonstrate that UCP1 does not protect against diet-induced obesity at thermoneutrality.NEW & NOTEWORTHY We provide evidence that the abundance of UCP1 does not influence energy metabolism at thermoneutrality studying a novel Cre-mediated UCP1-KO mouse model. This model will be a foundation for a better understanding of the contribution of UCP1 in different cell types or life stages to energy metabolism.

Dopamine receptor D1 signaling stimulates lipolysis and browning of white adipocytes.

Adipocytes express several kinds of catecholamine receptors, including adrenergic receptors, and dopamine receptors. Signaling pathways mediated by catecholamine receptors, such as ß3-adrenergic receptor pathway, can induce body energy expenditure via activating thermogenesis of adipose tissue. However, the roles of adipose dopamine receptors on adipocytes are still unclear. Here, we investigate the role of dopamine receptor D1 (DRD1) on adipocytes. To this end, we use DRD1 agonist Fenoldopam and antagonist SCH23390 to stimulate and inhibit DRD1 signaling, respectively. We found that, compared with control group mice, Fenoldopam-treated and SCH23390-treated high-fat-diet (HFD)-fed mice showed smaller and bigger white adipose tissue/adipocyte sizes, respectively. Meanwhile, activating of DRD1 signaling enhanced intracellular levels of cAMP, phosphorylation levels of protein kinase A substrates, and hormone-sensitive lipase, a key enzyme for lipolysis in mature 3T3-L1 adipocytes and white adipose tissue of HFD-fed mice. As a result, the levels of free fatty acid or glycerol were increased, indicating stimulation of lipolysis by DRD1 activation. Moreover, activating DRD1 can induce the browning of adipocytes, as indicated by enhanced phosphorylation of P38 MAP kinase, increased expression of beige cell markers (PGC-1α, UCP-1, and CD81), mitochondrion content, and expression of ß-oxidation related genes. All of these effects were reduced after treating with SCH23390 both in vitro and in HFD-fed mice. Collectively, our study indicated that DRD1 signaling stimulates lipolysis and browning of white adipocytes in vitro and in vivo. Understanding the functions of DRD1 on human adipocytes and adipose tissues will help us to design novel strategies to treat obesity.