Milk production and energy metabolism in ruminants fed 2-ketoisocaproate

Three trials were conducted to examine the effect of dietary 2-ketoisocaproate (KIC) supplementation on milk production and energy metabolism in ruminants. In the first two trials, 10 goats were fed either 0 or 1.1% calcium-KIC for 2 wk and 12 cows were fed either 0 or.75% sodium-KIC for 3 wk. Supplementation with KIC significantly increased milk fat content, milk fat yield, and 4% fat-corrected milk yield in cows by an average of 5, 10, and 8%, respectively, for the treatment period. In cows, response of milk fat yield to KIC was 14% during wk 1 of treatment but diminished to 7% by wk 3. Milk yield and milk protein yield tended to be greater in cows fed KIC, but milk production efficiency and body weight were unaltered in either species. In goats, supplementation with KIC had no significant effects on milk production or composition, but trends toward increased milk fat and protein content were observed;In the third trial, 30 mixed-breed growing lambs were fed a control diet or ruminally-protected leucine, KIC, or isovalerate at a molar equivalent of.05% leucine in the diet. Lambs were fed their respective diets for about 13 wk and slaughtered upon reaching 50 kg body weight. During wk 8, plasma glucose and acetate turnover rates were measured. Perirenal lipid deposition was decreased in lambs fed KIC by 45% (P \u3c.01) and tended to be decreased in lambs fed leucine by 29%. KIC also tended to decrease backfat thickness (25%, P \u3c.09). Leucine tended to decrease growth rate and efficiency of feed conversion when compared with KIC. Plasma glucagon concentration was less for lambs fed leucine, KIC, and isovalerate than for controls during wk 4 but not wk 8. Acetate flux tended to be greater in lambs fed KIC and leucine than in those fed isovalerate. Dietary treatment did not alter glucose concentration or flux or acetate concentration or oxidation rate;In summary, feeding KIC acutely stimulated milk fat production in lactating cows and decreased lipid deposition and plasma glucagon concentration in growing lambs. In growing lambs, the effect of KIC on lipid deposition was greater than that of either leucine or isovalerate. These results indicate that KIC may alter lipid metabolism in ruminants so that nutrients are partitioned away from body lipid stores and toward milk production

The Resilient Dairy Genome Project - a general overview of methods and objectives related to feed efficiency and methane emissions.

The Resilient Dairy Genome Project (RDGP) is an international large-scale applied research project that aims to generate genomic tools to breed more resilient dairy cows. In this context, improving feed efficiency and reducing greenhouse gases from dairy is a high priority. The inclusion of traits related to feed efficiency (e.g., dry matter intake [DMI]) or greenhouse gases (e.g., methane emissions [CH4]) relies on available genotypes as well as high quality phenotypes. Currently, 7 countries, i.e., Australia [AUS], Canada [CAN], Denmark [DNK], Germany [DEU], Spain [ESP], Switzerland [CHE], and United States of America [USA] contribute with genotypes and phenotypes including DMI and CH4. However, combining data is challenging due to differences in recording protocols, measurement technology, genotyping, and animal management across sources. In this study, we provide an overview of how the RDGP partners address these issues to advance international collaboration to generate genomic tools for resilient dairy. Specifically, we describe the current state of the RDGP database, data collection protocols in each country, and the strategies used for managing the shared data. As of February 2022, the database contains 1,289,593 DMI records from 12,687 cows and 17,403 CH4 records from 3,093 cows and continues to grow as countries upload new data over the coming years. No strong genomic differentiation between the populations was identified in this study, which may be beneficial for eventual across-country genomic predictions. Moreover, our results reinforce the need to account for the heterogeneity in the DMI and CH4 phenotypes in genomic analysis

Transcriptome Analysis of Epithelial and Stromal Contributions to Mammogenesis in Three Week Prepartum Cows

Transcriptome analysis of bovine mammary development has provided insight into regulation of mammogenesis. However, previous studies primarily examined expression of epithelial and stromal tissues combined, and consequently did not account for tissue specific contribution to mammary development. Our objective was to identify differences in gene expression in epithelial and intralobular stromal compartments. Tissue was biopsied from non-lactating dairy cows 3 weeks prepartum, cut into explants and incubated for 2 hr with insulin and hydrocortisone. Epithelial and intralobular stromal tissues were isolated with laser capture microdissection. Global gene expression was measured with Bovine Affymetrix GeneChips, and data were preprocessed using RMA method. Moderated t-tests from gene-specific linear model analysis with cell type as a fixed effect showed more than 3,000 genes were differentially expressed between tissues (P<0.05; FDR<0.17). Analysis of epithelial and stromal transcriptomes using Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathways Analysis (IPA) showed that epithelial and stromal cells contributed distinct molecular signatures. Epithelial signatures were enriched with gene sets for protein synthesis, metabolism and secretion. Stromal signatures were enriched with genes that encoded molecules important to signaling, extracellular matrix composition and remodeling. Transcriptome differences also showed evidence for paracrine interactions between tissues in stimulation of IGF1 signaling pathway, stromal reaction, angiogenesis, neurogenesis, and immune response. Molecular signatures point to the dynamic role the stroma plays in prepartum mammogenesis and highlight the importance of examining the roles of cell types within the mammary gland when targeting therapies and studying mechanisms that affect milk production

Milk production and energy metabolism in ruminants fed 2-ketoisocaproate

Three trials were conducted to examine the effect of dietary 2-ketoisocaproate (KIC) supplementation on milk production and energy metabolism in ruminants. In the first two trials, 10 goats were fed either 0 or 1.1% calcium-KIC for 2 wk and 12 cows were fed either 0 or.75% sodium-KIC for 3 wk. Supplementation with KIC significantly increased milk fat content, milk fat yield, and 4% fat-corrected milk yield in cows by an average of 5, 10, and 8%, respectively, for the treatment period. In cows, response of milk fat yield to KIC was 14% during wk 1 of treatment but diminished to 7% by wk 3. Milk yield and milk protein yield tended to be greater in cows fed KIC, but milk production efficiency and body weight were unaltered in either species. In goats, supplementation with KIC had no significant effects on milk production or composition, but trends toward increased milk fat and protein content were observed;In the third trial, 30 mixed-breed growing lambs were fed a control diet or ruminally-protected leucine, KIC, or isovalerate at a molar equivalent of.05% leucine in the diet. Lambs were fed their respective diets for about 13 wk and slaughtered upon reaching 50 kg body weight. During wk 8, plasma glucose and acetate turnover rates were measured. Perirenal lipid deposition was decreased in lambs fed KIC by 45% (P <.01) and tended to be decreased in lambs fed leucine by 29%. KIC also tended to decrease backfat thickness (25%, P <.09). Leucine tended to decrease growth rate and efficiency of feed conversion when compared with KIC. Plasma glucagon concentration was less for lambs fed leucine, KIC, and isovalerate than for controls during wk 4 but not wk 8. Acetate flux tended to be greater in lambs fed KIC and leucine than in those fed isovalerate. Dietary treatment did not alter glucose concentration or flux or acetate concentration or oxidation rate;In summary, feeding KIC acutely stimulated milk fat production in lactating cows and decreased lipid deposition and plasma glucagon concentration in growing lambs. In growing lambs, the effect of KIC on lipid deposition was greater than that of either leucine or isovalerate. These results indicate that KIC may alter lipid metabolism in ruminants so that nutrients are partitioned away from body lipid stores and toward milk production.</p

Circulating Metabolites Indicate Differences in High and Low Residual Feed Intake Holstein Dairy Cows

Selection for more feed efficient dairy cows is key to improving sustainability and profitability of dairy production; however, underlying mechanisms contributing to individual animal feed efficiency are not fully understood. The objective of this study was to identify circulating metabolites, and pathways associated with those metabolites, that differ between efficient and inefficient Holstein dairy cows using targeted metabolite quantification and untargeted metabolomics. The top and bottom fifteen percent of cows (n = 28/group) with the lowest and highest residual feed intake in mid-lactation feed efficiency trials were grouped retrospectively as high-efficient (HE) and low-efficient (LE). Blood samples were collected for quantification of energy metabolites, markers of hepatic function, and acylcarnitines, in addition to a broader investigation using untargeted metabolomics. Short-chain acylcarnitines, C3-acylcarnitine, and C4-acylcarntine were lower in HE cows (n = 18/group). Untargeted metabolomics and multivariate analysis identified thirty-nine differential metabolites between HE and LE (n = 8/group), of which twenty-five were lower and fourteen were higher in HE. Pathway enrichment analysis indicated differences in tryptophan metabolism. Combined results from targeted metabolite quantification and untargeted metabolomics indicate differences in fatty acid and amino acid metabolism between HE and LE cows. These differences may indicate post-absorptive nutrient use efficiency as a contributor to individual animal variation in feed efficiency

Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci.

Few studies have explored the impact of rare variants (minor allele frequency &lt; 1%) on highly heritable plasma metabolites identified in metabolomic screens. The Finnish population provides an ideal opportunity for such explorations, given the multiple bottlenecks and expansions that have shaped its history, and the enrichment for many otherwise rare alleles that has resulted. Here, we report genetic associations for 1391 plasma metabolites in 6136 men from the late-settlement region of Finland. We identify 303 novel association signals, more than one third at variants rare or enriched in Finns. Many of these signals identify genes not previously implicated in metabolite genome-wide association studies and suggest mechanisms for diseases and disease-related traits

Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices

Abstract Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids