EEF1A1 transcription cofactor gene polymorphism is associated with muscle gene expression and residual feed intake in Nelore cattle.

Cis-acting effects of noncoding variants on gene expression and regulatory molecules constitute a significant factor for phenotypic variation in complex traits. To provide new insights into the impacts of single-nucleotide polymorphisms (SNPs) on transcription factors (TFs) and transcription cofactors (TcoF) coding genes, we carried out a multi-omic analysis to identify cis-regulatory effects of SNPs on these genes' expression in muscle and describe their association with feed efficiency-related traits in Nelore cattle. As a result, we identified one SNP, the rs137256008C > T, predicted to impact the EEF1A1 gene expression (ß = 3.02; P-value = 3.51E-03) and the residual feed intake trait (ß = - 3.47; P-value = 0.02). This SNP was predicted to modify transcription factor sites and overlaps with several QTL for feed efficiency traits. In addition, co-expression network analyses showed that animals containing the T allele of the rs137256008 SNP may be triggering changes in the gene network. Therefore, our analyses reinforce and contribute to a better understanding of the biological mechanisms underlying gene expression control of feed efficiency traits in bovines. The cis-regulatory SNP can be used as biomarker for feed efficiency in Nelore cattle.

Genetic effects of heat stress on milk fatty acids in Brazilian Holstein cattle.

The present study aimed to estimate covariance components of milk fatty acids (FA) and to compare the genomic estimated breeding values under general and heat-stress effects. Data consisted of 38,762 test-day records from 6,344 Holstein cows obtained from May 2012 through January 2018 on 4 dairy herds from Brazil. Single-trait repeatability test-day models with random regressions as a function of temperature-humidity index values were used for genetic analyses. The models included contemporary groups, parity order (1-6), and days in milk classes as fixed effects, and general and thermotolerance additive genetic and permanent environmental as random effects. Notably, differences in heritability estimates between environments (general and heat stress) increased (0.03 to 0.06) for unsaturated FA traits, such as unsaturated, monounsaturated, and polyunsaturated, at higher heat-stress levels. In contrast, heritability estimated between environments for saturated FA traits, including saturated FA, palmitic acid (C16:0), and stearic acid (C18:0) did not observe significant differences between environments. In addition, our study revealed negative genetic correlations between general and heat-stress additive genetic effects (antagonistic effect) for the saturated FA, C16:0, C18:0, and C18:1, which ranged from -0.007 to -0.32. Spearman's ranking correlation between genomic estimated breeding values ranged from -0.27 to 0.99. Results indicated a moderate to strong interaction of genotype by the environment for most FA traits comparing a heat-stress environment with thermoneutral conditions. Our findings point out novel opportunities to explore the use of FA milk profile and heat-stress models.

Gradual weaning does not improve performance for calves with low starter intake at the beginning of the weaning process.

The weaning process may cause intense stress for dairy calves, even when low volumes of liquid diet are fed. Management tools that increase the intake of solid feeds, such as gradual weaning, can provide better physiological and metabolic conditions through better ruminal development, leading to better adaptation to ruminant metabolism and aiding in stress mitigation. The objective of this study was to evaluate the effects of 2 weaning protocols and 2 levels of concentrate intake on the performance and physiological and behavioral variables related to stress in dairy calves. Thirty-six newborn male Holstein calves were used in a randomized block design with a 2 × 2 factorial arrangement: 2 weaning strategies, abrupt or gradual, and 2 levels of concentrate intake at 5 wk of age, high (>350 g/d) or low (≤350 g/d). Calves were equally managed until they were 5 wk of age and then grouped according to concentrate intake. Statistical analyzes were performed using the MIXED procedure of SAS software (SAS Institute Inc., Cary, NC), and no significant interaction was observed between studied factors (weaning method and starter intake level); therefore, we considered each factor separately and their interactions with age. The highest dry matter intake and concentration of ß-hydroxybutyrate were recorded for animals with a high level of starter intake independent of the weaning method. Structural growth (cm/wk) and average daily gain were superior for calves with high starter intake, but weaning method had no effect. The gradual weaning protocol increased the time eating starter, regardless of the level of concentrate intake. Even animals with low concentrate intake that were weaned abruptly showed levels of cortisol and acid-soluble glycoprotein within normal physiological levels. Apparently, other factors besides the milk supply affect the starter intake level of calves in a conventional feeding program. The adoption of gradual weaning is not effective in improving performance when a calf has low intake 3 wk before weaning is complete, but it reduced vocalization on d 2 postweaning.

Genome-wide association study for milk production traits in a Brazilian Holstein population.

Advances in the molecular area of selection have expanded knowledge of the genetic architecture of complex traits through genome-wide association studies (GWAS). Several GWAS have been performed so far, but confirming these results is not always possible due to several factors, including environmental conditions. Thus, our objective was to identify genomic regions associated with traditional milk production traits, including milk yield, somatic cell score, fat, protein and lactose percentages, and fatty acid composition in a Holstein cattle population producing under tropical conditions. For this, 75,228 phenotypic records from 5,981 cows and genotypic data of 56,256 SNP from 1,067 cows were used in a weighted single-step GWAS. A total of 46 windows of 10 SNP explaining more than 1% of the genetic variance across 10 Bos taurus autosomes (BTA) harbored well-known and novel genes. The MGST1 (BTA5), ABCG2 (BTA6), DGAT1 (BTA14), and PAEP (BTA11) genes were confirmed within some of the regions identified in our study. Potential novel genes involved in tissue damage and repair of the mammary gland (COL18A1), immune response (LTTC19), glucose homeostasis (SLC37A1), synthesis of unsaturated fatty acids (LTBP1), and sugar transport (SLC37A1 and MFSD4A) were found for milk yield, somatic cell score, fat percentage, and fatty acid composition. Our findings may assist genomic selection by using these regions to design a customized SNP array to improve milk production traits on farms with similar environmental conditions.

Estimates of genomic heritability and genome-wide association study for fatty acids profile in Santa Inês sheep.

BACKGROUND: Despite the health concerns and nutritional importance of fatty acids, there is a relative paucity of studies in the literature that report genetic or genomic parameters, especially in the case of sheep populations. To investigate the genetic architecture of fatty acid composition of sheep, we conducted genome-wide association studies (GWAS) and estimated genomic heritabilities for fatty acid profile in Longissimus dorsi muscle of 216 male sheep. RESULTS: Genomic heritability estimates for fatty acid content ranged from 0.25 to 0.46, indicating that substantial genetic variation exists for the evaluated traits. Therefore, it is possible to alter fatty acid profiles through selection. Twenty-seven genomic regions of 10 adjacent SNPs associated with fatty acids composition were identified on chromosomes 1, 2, 3, 5, 8, 12, 14, 15, 16, 17, and 18, each explaining ≥0.30% of the additive genetic variance. Twenty-three genes supporting the understanding of genetic mechanisms of fat composition in sheep were identified in these regions, such as DGAT2, TRHDE, TPH2, ME1, C6, C7, UBE3D, PARP14, and MRPS30. CONCLUSIONS: Estimates of genomic heritabilities and elucidating important genomic regions can contribute to a better understanding of the genetic control of fatty acid deposition and improve the selection strategies to enhance meat quality and health attributes.

Intensive liquid feeding of dairy calves with a medium crude protein milk replacer: Effects on performance, rumen, and blood parameters.

The objective of this study was to evaluate the effects of different liquid-feeding systems using a medium crude protein milk replacer on performance, rumen, and blood parameters. Thirty newborn Holstein calves were blocked according to birth weight and date of birth, and randomly distributed to different liquid-feeding systems: conventional (4 L/d), intensive (8 L/d), or step-up/step-down (wk 1, 4 L/d; wk 2 to 6, 8 L/d; wk 7 and 8, 4 L/d). The commercial milk replacer (12.5% solids, 20.2% crude protein, 15.6% fat) was fed twice daily (0700 and 1700 h) until calves were weaned, at 8 wk of age. Calves were individually housed in wood hutches, with free access to water and starter concentrate, and to hay only after weaning. They were followed through 10 wk of age. Milk replacer and starter intake were inversely affected by feeding system. After weaning, starter intake and hay intake were similar among feeding systems. Total dry matter intake was higher during the liquid-feeding period for calves on the intensive system compared to calves on the conventional system, but conventional feeding resulted in the highest dry matter intake after weaning. Feed efficiency was similar among feeding systems before and after weaning. Average body weight and daily gain were not affected by feeding system before or after weaning. During liquid feeding, diarrhea occurrence was lower for calves on the conventional system; however, when calves on the step-up/step-down system were fed lower volumes of liquid feed, diarrhea occurrence was similar to that of calves on the conventional system. Plasma concentrations of ß-hydroxybutyrate were higher for calves on the conventional system, reflecting starter intake. Rumen pH, short-chain fatty acids, and N-NH3 were not affected by feeding system. Feeding higher volumes of milk replacer with a medium crude protein content had no beneficial effect on the performance of calves up to 10 wk of age.

Do different standard plate counting (IDF/ISSO or AOAC) methods interfere in the conversion of individual bacteria counts to colony forming units in raw milk?

AIMS: This study aimed to establish the correlation between individual bacterial count (IBC) obtained by flow cytometry and the number of colony forming units (CFU) determined by standard plate count (SPC) in raw milk using two different reference methodologies: the methodology of the International Dairy Federation (IDF) - International Organization for Standardization (ISO) 4833, incubation for 72 h at 30°C and the methodology of the Association of Official Analytical Chemists (AOAC), incubation for 48 h at 35°C. METHODS AND RESULTS: For this, 100 bovine milk samples (80 ml) from different farms were collected in a sterile bottle and maintained refrigerated at 4°C and were delivered to the laboratory. In the laboratory, the samples were divided into two vials of 40 ml each. Then, half of the vials were forwarded for the SPC analysis, and the other half were analysed using the equipment BactoScan FC. The analyses by flow cytometry and SPC were performed at the same time (maximum deviation of +/- 1 h). To transform the data from IBC ml(-1) to CFU ml(-1) (IDF or AOAC methodology), a standard linear regression equation was used, as recommended by IDF/ISO-196. The difference between the reference methodologies affects the equation that transforms IBC into CFU and therefore the accuracy of the results. The results estimated by the equation using the ISO 4833 methodology were on average 0·18 log units higher than the results estimated using the equation using the AOAC methodology. CONCLUSIONS: After the comparison of the methodologies, it was concluded that there is an impact of the reference methodologies on the conversion of the results from IBC to CFU. SIGNIFICANCE AND IMPACT OF THE STUDY: Depending on the methodology adopted by each laboratory or country, there may not be equivalence in the results. Hence, the laboratories specialized in milk quality analysis that have changed their methodology for analysis, passing from the MAPA (AOAC) methodology to the IDF standard, need to develop new conversion equations to make their results in CFU ml(-1) consistent regardless of the reference methodology.

Bovine epididymal spermatozoa: Resistance to cryopreservation and binding ability to oviductal cells.

In this study we examined quality, longevity and ability of epididymal sperm (EP) to bind to oviduct explants (OE) after cooling and cryopreservation. Ejaculated (EJ) and EP sperm from seven bulls were evaluated before, during and after cryopreservation for total (TM), progressive motility (PM), sperm morphology, plasma membrane integrity (PMI) and acrosome integrity (ACI). For longevity, cryopreserved EP, EJ and a third group of cells in which EP spermatozoa were incubated with seminal plasm (SP) for 10 min after thawing (EPP group), were compared, and the groups were analyzed at 0, 3, 6, and 24 h for all parameters. Sperm from each group were co-incubated with OE for 30 min, 6 h, and 24 h for binding evaluation. Data were analyzed by the generalized linear models SAS 9.1 (P < 0.05). After cooling, EP displayed higher TM, higher PMI, and higher ACI (P < 0.05) than EJ. No differences were noted in the percentage of spermatozoa with PMI and AI between EJ and EP for fresh, cooled or cryopreserved sperm. However, a reduction in motility occurred in the EJ sperm after cooling, while in EP group such reduction occurred only after cryopreservation. At 6 h of incubation EP and EPP had higher PMI and ACI than EJ (P < 0.05). The number of spermatozoa bound to OE was similar P > 0.05) for all groups either at 30 min or 24 h. We conclude that EP are more resistant to cooling than EJ, and can bind to OE similarly to EJ.

Variation in myogenic differentiation 1 mRNA abundance is associated with beef tenderness in Nelore cattle.

The myogenic differentiation 1 gene (MYOD1) has a key role in skeletal muscle differentiation and composition through its regulation of the expression of several muscle-specific genes. We first used a general linear mixed model approach to evaluate the association of MYOD1 expression levels on individual beef tenderness phenotypes. MYOD1mRNA levels measured by quantitative polymerase chain reactions in 136 Nelore steers were significantly associated (P ≤ 0.01) with Warner-Bratzler shear force, measured on the longissimus dorsi muscle after 7 and 14 days of beef aging. Transcript abundance for the muscle regulatory gene MYOD1 was lower in animals with more tender beef. We also performed a co-expression network analysis using whole transcriptome sequence data generated from 30 samples of longissimus muscle tissue to identify genes that are potentially regulated by MYOD1. The effect of MYOD1 gene expression on beef tenderness may emerge from its function as an activator of muscle-specific gene transcription such as for the serum response factor (C-fos serum response element-binding transcription factor) gene (SRF), which determines muscle tissue development, composition, growth and maturation.

A single nucleotide polymorphism in NEUROD1 is associated with production traits in Nelore beef cattle.

Feed efficiency and carcass characteristics are late-measured traits. The detection of molecular markers associated with them can help breeding programs to select animals early in life, and to predict breeding values with high accuracy. The objective of this study was to identify polymorphisms in the functional and positional candidate gene NEUROD1 (neurogenic differentiation 1), and investigate their associations with production traits in reference families of Nelore cattle. A total of 585 steers were used, from 34 sires chosen to represent the variability of this breed. By sequencing 14 animals with extreme residual feed intake (RFI) values, seven single nucleotide polymorphisms (SNPs) in NEUROD1 were identified. The investigation of marker effects on the target traits RFI, backfat thickness (BFT), ribeye area (REA), average body weight (ABW), and metabolic body weight (MBW) was performed with a mixed model using the restricted maximum likelihood method. SNP1062, which changes cytosine for guanine, had no significant association with RFI or REA. However, we found an additive effect on ABW (P ≤ 0.05) and MBW (P ≤ 0.05), with an estimated allele substitution effect of -1.59 and -0.93 kg0.75, respectively. A dominant effect of this SNP for BFT was also found (P ≤ 0.010). Our results are the first that identify NEUROD1 as a candidate that affects BFT, ABW, and MBW. Once confirmed, the inclusion of this SNP in dense panels may improve the accuracy of genomic selection for these traits in Nelore beef cattle as this SNP is not currently represented on SNP chips.

Genetic parameters for milk fatty acids, milk yield and quality traits of a Holstein cattle population reared under tropical conditions.

Information about genetic parameters is essential for selection decisions and genetic evaluation. These estimates are population specific; however, there are few studies with dairy cattle populations reared under tropical and sub-tropical conditions. Thus, the aim was to obtain estimates of heritability and genetic correlations for milk yield and quality traits using pedigree and genomic information from a Holstein population maintained in a tropical environment. Phenotypic records (n = 36 457) of 4203 cows as well as the genotypes for 57 368 single nucleotide polymorphisms from 755 of these cows were used. Covariance components were estimated using the restricted maximum likelihood method under a mixed animal model, considering a pedigree-based relationship matrix or a combined pedigree-genomic matrix. High heritabilities (around 0.30) were estimated for lactose and protein content in milk whereas moderate values (between 0.19 and 0.26) were obtained for percentages of fat, saturated fatty acids and palmitic acid in milk. Genetic correlations ranging from -0.38 to -0.13 were determined between milk yield and composition traits. The smaller estimates compared to other similar studies can be due to poor environmental conditions, which may reduce genetic variability. These results highlight the importance in using genetic parameters estimated in the population under evaluation for selection decisions.

Genome scan for meat quality traits in Nelore beef cattle.

Meat quality traits are economically important because they affect consumers' acceptance, which, in turn, influences the demand for beef. However, selection to improve meat quality is limited by the small numbers of animals on which meat tenderness can be evaluated due to the cost of performing shear force analysis and the resultant damage to the carcass. Genome wide-association studies for Warner-Bratzler shear force measured at different times of meat aging, backfat thickness, ribeye muscle area, scanning parameters [lightness, redness (a*), and yellowness] to ascertain color characteristics of meat and fat, water-holding capacity, cooking loss (CL), and muscle pH were conducted using genotype data from the Illumina BovineHD BeadChip array to identify quantitative trait loci (QTL) in all phenotyped Nelore cattle. Phenotype count for these animals ranged from 430 to 536 across traits. Meat quality traits in Nelore are controlled by numerous QTL of small effect, except for a small number of large-effect QTL identified for a*fat, CL, and pH. Genomic regions harboring these QTL and the pathways in which the genes from these regions act appear to differ from those identified in taurine cattle for meat quality traits. These results will guide future QTL mapping studies and the development of models for the prediction of genetic merit to implement genomic selection for meat quality in Nelore cattle.

Expression of 1alpha-HYD and 24-HYD in bovine kidney mediated by vitamin D3 supplementation.

In order to better understand vitamin D3 in cattle metabolism, we quantified 1alpha-HYD and 24-HYD gene expression. In the kidneys of 35 male Nellore cattle, these were divided into a control group and two treatment groups (2 x 10(6) international units of vitamin D3 administered for 2 or 8 consecutive days pre-slaughter). Vitamin D3 supplementation resulted in a significant increase in 1alpha-HYD gene expression; however, significantly increased 24-HYD gene expression was only detected in cattle that had 8 days of supplementation. The finding of upregulation of 24-HYD due to vitamin D supplementation is in line with the expected rise in 24,25-di-hydroxy-vitamin D3 synthesis observed when plasma vitamin D3 concentrations are high, stimulating excretion by the organism. On the other hand, upregulation of 1alpha-HYD was unexpected, since vitamin D3 supplementation has been reported to impact these two genes in opposite directions. We conclude that vitamin D3 metabolism in these animals is more complex than previously reported.

Single nucleotide polymorphisms in the growth hormone and IGF type-1 (IGF1) genes associated with carcass traits in Santa Ines sheep.

Polymorphisms in the growth hormone (GH) and IGF type-1 (IGF1) genes have been associated with the economic traits in farm animals, including BW of some sheep breeds. However, it remains unknown if these polymorphisms also affect carcass traits in sheep. Thus, we aimed to identify polymorphisms in the GH and IGF1 genes in Santa Ines sheep in order to describe their allelic and genotypic frequencies as well as to test the hypotheses that they are associated with the carcass traits. Fragments of 4550 bp (IGF1) and 1194 bp (GH) were sequenced in up to 191 lambs. In all, 18 polymorphisms were identified in the IGF1 and 21 in the GH gene. The IGF1 polymorphisms rs430457475, rs412470350, rs409110739 and rs400113576 showed an additive effect on the internal carcass length (-0.9265±0.4223), rump girth (-2.9285±1.1473), rib yield (-1.0003±0.4588) and neck weight (-0.0567±0.0278), respectively. In addition, the polymorphisms rs58957314 in the GH affected the rib weight (-0.4380±0.1272) and rib yield (-2.2680±0.6970), loin weight (-0.1893±0.0516) and loin yield (-0.9423±0.3259), palette weight (-0.2265±0.0779) and palette yield (-0.9424±0.4184), leg weight (-0.3960±0.1375), neck weight (-0.0851±0.0394) and carcass finishing score (-0.1700±0.0839). These results allow us to conclude that there are polymorphisms in the IGF1 and GH genes associated with carcass traits in Santa Ines sheep, which can provide important information for marker-assisted selection.

Molecular basis for porcine parvovirus detection in dead fetuses.

Reproductive failures are still common grounds for complaint by commercial swine producers. Porcine parvovirus (PPV) is associated with different clinical reproductive signs. The aim of the present study was to investigate PPV fetal infection at swine farms having ongoing reproductive performance problems. The presence of virus in fetal tissues was determined by nested-polymerase chain reaction assay directed to the conserved NS1 gene of PPV in aborted fetuses, mummies and stillborns. Fetuses show a high frequency of PPV infection (96.4%; n = 28). In 60.7% of the fetuses, PPV were detected in all tissue samples (lung, heart, thymus, kidney, and spleen). Viral infection differed among fetal tissues, with a higher frequency in the lung and heart (p < 0.05). Fetuses with up to 99 days of gestational age and from younger sows showed a higher frequency of PPV (p < 0.05). No significant difference in the presence of PPV was detected among the three clinical presentations. The results suggest that PPV remains an important pathogenic agent associated with porcine fetal death.

Non-additive genetic effects on weights and performance of a Brazilian Bos taurus x Bos indicus beef composite.

The aim of the present study was to evaluate the heterosis effects on weaning weight at 205 days (WW, n = 146,464), yearling weight at 390 days (YW, n = 69,315) and weight gain from weaning to yearling (WG, n = 59,307) in composite beef cattle. The fixed models were: RM, which included contemporary groups, class of age of dam, outcrossing percentages for direct and maternal effects, and additive direct and maternal (AM) breed effects; R, RM model, minus AM breed effects, and H, RM model, minus additive breed effects. The estimates for W205 were in general positive (P < 0.01). The R and H models resulted in similar estimates, but they were very different from the ones estimated by the RM model. For W390, the R and H models resulted in general positive estimates (P < 0.05). For WG, the RM model resulted in general significant heterosis effects (P < 0.05). It can be concluded that the RM model seems to supply estimates of better quality (P < 0.01).

Genetic trend estimates of meat quality traits in a male broiler line.

The present research was conducted to estimate the genetic trends for meat quality traits in a male broiler line. The traits analyzed were initial pH, pH at 6 h after slaughter, final pH, initial range of falling pH, final range of falling pH, lightness, redness, yellowness, weep loss, drip loss, shrink loss, and shear force. The number of observations varied between 618 and 2125 for each trait. Genetic values were obtained by restricted maximum likelihood, and the numerator relationship matrix had 107,154 animals. The genetic trends were estimated by regression of the broiler average genetic values with respect to unit of time (generations), and the average genetic trend was estimated by regression coefficients. Generally, for the traits analyzed, small genetic trends were obtained, except for drip loss and shear force, which were higher. The small magnitude of the trends found could be a consequence of the absence of selection for meat quality traits in the line analyzed. The estimates of genetic trends obtained were an indication of an improvement in the meat quality traits in the line analyzed, except for drip loss.

Genetic parameters for growth traits of a Brazilian Bos taurus x Bos indicus beef composite.

The genetic analysis of composite data is very complicated, mainly because it is necessary to adjust data to the effects of heterosis and breed complementarity, and because there is usually considerable confounding of these data with several other effects, such as contemporary group effects, breed composition of the animal and maternal breed composition, among others. Data on birth weight (n = 151,083), weaning weight adjusted to 205 days (n = 137,257), yearling weight adjusted to 390 days (n = 61,410), weight gain from weaning to yearling (n = 56,653), and scrotum circumference (n = 23,323) and muscle score (n = 54,770), both adjusted to 390 days, from Bos taurus x Bos indicus composite beef calves born from 1994 to 2003 were analyzed to estimate (co)variance components and genetic parameters of growth traits. The animals belonged to the Montana Tropical program. Estimation was made by three models that approach adjustment to heterozygosis in order to suggest the best model. The RM model included contemporary groups, class of age of dam, outcrossing percentages for direct and maternal effects, and direct and maternal additive genetic breed effects as covariates; the R model was the same as RM, but without additive maternal breed effects, and H was the same as RM, but not considering any additive breed effect. Both R2 values and consistency of genetic parameters indicate that the more complex model (RM), which considers maternal and individual additive genetic breed effect, produces the best estimates when compared to other models. The R model seems to overestimate (co)variance components. The magnitudes of direct and maternal heritability estimates, obtained in this study, would permit genetic improvement for weight and growth traits, as much by selection of direct genetic effects for weight and growth as for the improvement of maternal performance, but in different lineages. Therefore, the correlations between these effects were unfavorable.

Genetic trends of absolute and relative heart weight in a male broiler line.

Data of chickens from a broiler-breeding program have been collected and used for determination of genetic trends of absolute and relative heart weight. The genetic trends have been estimated by regression of the genetic values of the traits over hatch-year. Genetic values of 42,912 individuals, obtained by restricted maximum likelihood, were used for regression analysis. The estimates of the genetic trends for absolute and relative heart weight were found to be -0.08 g and -0.004% per hatch-year, respectively. These trends show that heart weight in the line analyzed, in absolute and relative terms, has tended to decrease, which can make the metabolic disorders due to the reduction in heart weight in broilers even worse.

Investigation of mechanisms involved in regulation of progesterone catabolism using an overfed versus underfed ewe-lamb model.

Alterations in progesterone (P4) catabolism due to high feed intake underlie some effects of nutrition on reproduction. Based on previous research, we hypothesized that high feed intake could potentially increase P4 catabolism, likely due to increased liver blood flow. However, there could also be an opposing action due to increased circulating insulin, which has been shown to inhibit hepatic expression of key enzymes involved in P4 catabolism. To test which effect would have the greatest impact on circulating P4 during a 1- and 2 -mo time frame, we used a noncyclic ewe model. The plane of nutrition was controlled, and effects on circulating insulin, P4 catabolism in response to exogenous P4, and steady state mRNA for key hepatic enzymes were evaluated. Twenty-four F Dorper × Santa Inês ewe lambs (5 mo old and approximately 25 kg BW) were used. After 14 d of adaptation, ewes were randomized into 2 groups: ad libitum fed (Ad), with intake of 3.8% DM/kg BW, or restricted feed intake (R), with 2% DM/kg BW, for 8 wk. At wk 4 and 8, ewes received an intravaginal P4 implant to evaluate P4 catabolism. As designed, Ad ewes had greater daily feed intake than R ewes (means of 1.8 [SE 0.03] and 0.6 kg/ewe [SE 0.01]; < 0.001) and greater weekly gain in BW (means of 1.7 [SE 0.12] vs. -0.1 kg/ewe [SE 0.03]; < 0.001). Mean circulating insulin of samples collected from -0.5 to 7 h after the start of feeding was over 5-fold greater in Ad ewes than in R ewes (least squares means of 8.2 [SE 0.93] vs. 1.5 µIU/mL [SE 0.16], respectively, at wk 4 and 12.0 [SE 1.02] vs. 2.2 µIU/mL [SE 0.18], respectively, at wk 8; < 0.001). Although both groups received the same P4 treatment, mean circulating P4 of samples collected from -0.5 to 7 h after feeding was much lower in Ad ewes than in R ewes (least squares means of 3.2 [SE 0.32] vs. 5.5 ng/mL [SE 0.32], respectively, at wk 4 and 2.8 [SE 0.28] vs. 5.2 ng/mL [SE 0.28], respectively, at wk 8; < 0.001) indicating much greater P4 catabolism in ewes with high feed intake. Unexpectedly, there was no effect of diet on hepatic mRNA concentrations for , , , or at wk 4 or 8 in spite of dramatically elevated insulin. Therefore, high energy/feed intake primarily increased P4 catabolism with no evidence for offsetting effects due to insulin-induced changes in hepatic P4 metabolizing enzymes.