Metabolic and Endocrine Role of Adipose Tissue During Lactation.

The adipose tissue serves an essential role for survival and reproduction in mammals, especially females. It serves primarily as an energy storage organ and is directly linked to the reproductive success of mammals. In wild animals, adipose tissue function is linked to seasonality of the food supply to support fetal growth and milk production. Adipose tissue depots in ruminants and non-ruminants can secrete many signal molecules (adipokines) that act as hormones and as pro- and anti-inflammatory cytokines. The visceral adipose tissue especially appears to be more endocrinologically active than other adipose depots. The endocrine function is important for the overall long-term regulation of energy metabolism and plays an important role in the adaptation to lactation in many mammalian species, including humans. Furthermore, endocrine signals from adipose tissue depots contribute to fertility modulation, immune function, and inflammatory response. Energy homeostasis is modulated by changes in feed intake, insulin sensitivity, and energy expenditure, processes that can be influenced by adipokines in the brain and in peripheral tissues.

Analysis of pasture supplementation strategies by means of a mechanistic model of ruminal digestion and metabolism in the dairy cow.

Effective pasture supplementation is critical to the efficiency of resource management in milk production. We understand a great deal about ruminal and metabolic processes in dairy cattle that control efficiency but we need to improve our ability to predict effects of practical feeding strategies based on the basic biological processes of the cow. Therefore, a large-scale pasture supplementation study was used to explore the details of both practical management and the underlying biological principles and processes involved. This included a multiple lactation study coupled with shorter-term experiments that tested the type and rate of supplementation. Basal supplementation strategies were (1) pasture allowance [14 kg of dry matter (DM)/d per cow] supplemented with milled barley grain fed twice daily in the milking parlor and pasture silage provided in the paddock; the ratio of grain:forage fed as supplement was 0.75:0.25 (control; DM basis); (2) the same pasture allowance plus the same amounts of milled barley grain and pasture silage, but the supplements were mixed and chopped before being fed immediately after each milking; and (3) the same pasture allowance and offered a partial mixed ration comprising barley (25%) and corn grain (30% of DM), corn silage (20% of DM), and alfalfa hay (25% of DM) after each milking. In late lactation (227 d in milk), a short-term experiment was done feeding the same pasture allowances but with the 3 supplements offered at 6, 8, 10, and 12 kg of DM/d for an 11-d measurement period following adaptation to the diet to each of the 3 long-term supplementation groups. Production responses were recorded and ruminal volatile fatty acids (VFA) and pH were measured in a subset of animals. Model descriptions of yields of milk and milk constituents as well as mean concentrations of ruminal fluid VFA and ruminal fluid pH were compared with measured values resulting when dairy cows were fed 12 different pasture-based diets with different levels and types of dietary supplement. Inputs into the model were measured dry matter intake and feed composition on the 12 combined treatments as well as initial body weight and composition. The model described milk and milk component production within 1 standard deviation of the treatment means (less than 5% of the mean as measured in the root mean square error). The simulated proportions of ruminal acetate, propionate, and butyrate were consistent with observed effects of supplemental treatments and rate of supplementation; however, the error analysis showed room for improvement. The model described, to a general extent, the changes in ruminal pH; however, this investigation showed that the equations that describe ruminal pH need to be improved or modified. These results show that the fundamental knowledge of ruminal and organ metabolism in this mechanistic model is sufficient to describe the qualitative responses to complicated dietary strategies, but our quantitative understanding of the parameters involved such as degradation and absorption kinetics and ruminal pH still demands more specific research.

Invited review: Experimental design, data reporting, and sharing in support of animal systems modeling research.

The National Animal Nutrition Program "National Research Support Project 9" supports efforts in livestock nutrition, including the National Research Council's committees on the nutrient requirements of animals. Our objective was to review the status of experimentation and data reporting in animal nutrition literature and to provide suggestions for the advancement of animal nutrition research and the ongoing improvement of field-applied nutrient requirement models. Improved data reporting consistency and completeness represent a substantial opportunity to improve nutrition-related mathematical models. We reviewed a body of nutrition research; recorded common phrases used to describe diets, animals, housing, and environmental conditions; and proposed equivalent numerical data that could be reported. With the increasing availability of online supplementary material sections in journals, we developed a comprehensive checklist of data that should be included in publications. To continue to improve our research effectiveness, studies utilizing multiple research methodologies to address complex systems and measure multiple variables will be necessary. From the current body of animal nutrition literature, we identified a series of opportunities to integrate research focuses (nutrition, reproduction and genetics) to advance the development of nutrient requirement models. From our survey of current experimentation and data reporting in animal nutrition, we identified 4 key opportunities to advance animal nutrition knowledge: (1) coordinated experiments should be designed to employ multiple research methodologies; (2) systems-oriented research approaches should be encouraged and supported; (3) publication guidelines should be updated to encourage and support sharing of more complete data sets; and (4) new experiments should be more rapidly integrated into our knowledge bases, research programs and practical applications.

A dynamic, mechanistic model of metabolism in adipose tissue of lactating dairy cattle.

Research in dairy cattle biology has resulted in a large body of knowledge on nutrition and metabolism in support of milk production and efficiency. This quantitative knowledge has been compiled in several model systems to balance and evaluate rations and predict requirements. There are also systems models for metabolism and reproduction in the cow that can be used to support research programs. Adipose tissue plays a significant role in the success and efficiency of lactation, and recent research has resulted in several data sets on genomic differences and changes in gene transcription of adipose tissue in dairy cattle. To fully use this knowledge, we need to build and expand mechanistic, dynamic models that integrate control of metabolism and production. Therefore, we constructed a second-generation dynamic, mechanistic model of adipose tissue metabolism of dairy cattle. The model describes the biochemical interconversions of glucose, acetate, ß-hydroxybutyrate (BHB), glycerol, C16 fatty acids, and triacylglycerols. Data gathered from our own research and published references were used to set equation forms and parameter values. Acetate, glucose, BHB, and fatty acids are taken up from blood. The fatty acids are activated to the acyl coenzyme A moieties. Enzymatically catalyzed reactions are explicitly described with parameters including maximal velocity and substrate sensitivity. The control of enzyme activity is partially carried out by insulin and norepinephrine, portraying control in the cow. Model behavior was adequate, with sensitive responses to changing substrates and hormones. Increased nutrient uptake and increased insulin stimulate triacylglycerol synthesis, whereas a reduction in nutrient availability or increase in norepinephrine increases triacylglycerol hydrolysis and free fatty acid release to blood. This model can form a basis for more sophisticated integration of existing knowledge and future studies on metabolic efficiency of dairy cattle.

TRIENNIAL LACTATION SYMPOSIUM: Systems biology of regulatory mechanisms of nutrient metabolism in lactation.

A major role of the dairy cow is to convert low-quality plant materials into high-quality protein and other nutrients for humans. We must select and manage cows with the goal of having animals of the greatest efficiency matched to their environment. We have increased efficiency tremendously over the years, yet the variation in productive and reproductive efficiency among animals is still large. In part, this is because of a lack of full integration of genetic, nutritional, and reproductive biology into management decisions. However, integration across these disciplines is increasing as the biological research findings show specific control points at which genetics, nutrition, and reproduction interact. An ordered systems biology approach that focuses on why and how cells regulate energy and N use and on how and why organs interact through endocrine and neurocrine mechanisms will speed improvements in efficiency. More sophisticated dairy managers will demand better information to improve the efficiency of their animals. Using genetic improvement and animal management to improve milk productive and reproductive efficiency requires a deeper understanding of metabolic processes throughout the life cycle. Using existing metabolic models, we can design experiments specifically to integrate data from global transcriptional profiling into models that describe nutrient use in farm animals. A systems modeling approach can help focus our research to make faster and larger advances in efficiency and determine how this knowledge can be applied on the farms.

Cow-calf reproductive, genetic, and nutritional management to improve the sustainability of whole beef production systems.

Optimizing efficiency in the cow-calf sector is an important step toward improving beef sustainability. The objective of the study was to use a model to identify the relative roles of reproductive, genetic, and nutritional management in minimizing beef production systems' environmental impact in an economically viable, socially acceptable manner. An economic and environmental diet optimizer was used to identify ideal nutritional management of beef production systems varying in genetic and reproductive technology use. Eight management scenarios were compared to a least cost baseline: average U.S. production practices (CON), CON with variable nutritional management (NUT), twinning cattle (TWN), early weaning (EW), sire selection by EPD using either on-farm bulls (EPD-B) or AI (EPD-AI), decreasing the calving window (CW), or selecting bulls by EPD and reducing the calving window (EPD-CW). Diets to minimize land use, water use, and/or greenhouse gas (GHG) emissions were optimized under each scenario. Increases in diet cost attributable to reducing environmental impact were constrained to less than stakeholder willingness to pay for improved efficiency and reduced environmental impact. Baseline land use, water use, and GHG emissions were 188 m, 712 L, and 21.9 kg/kg HCW beef. The NUT scenario, which assessed opportunities to improve sustainability by altering nutritional management alone, resulted in a simultaneous 1.5% reduction in land use, water use, and GHG emissions. The CW scenario improved calf uniformity and simultaneously decreased land use, water use, and GHG emissions by 3.2%. Twinning resulted in a 9.2% reduction in the 3 environmental impact metrics. The EW scenario allowed for an 8.5% reduction in the 3 metrics. The EPD-AI scenario resulted in an 11.1% reduction, which was comparable to the 11.3% reduction achieved by EPD-B in the 3 metrics. Improving genetic selection by using AI or by purchasing on-farm bulls based on their superior EPD demonstrated clear opportunity to improve sustainability. When genetic and reproductive technologies were adopted, up to a 12.4% reduction in environmental impact was achievable. Given the modeling assumptions used in this study, optimizing nutritional management while concurrently improving genetic and reproductive efficiency may be promising avenues to improve productivity and sustainability of U.S. beef systems.

Efficiency of use of metabolizable energy for body weight gain in pasture-based, nonlactating dairy cows.

Four cohorts of nonlactating, pregnant dairy cows (n=50, 47, 45, and 42) were individually fed indoors to determine the amount of feed required for body weight (BW) gain from autumn pasture and commonly used supplementary feeds. These results were used to estimate the apparent efficiency with which metabolizable energy (ME) is used for BW gain (app_kg). Control cows were offered autumn pasture to estimated maintenance requirements (~0.55 MJ of ME/kg of BW(0.75)), with an additional 20 MJ of ME/d allocated for pregnancy and activity. All other cows received the same allowance of autumn pasture and an additional allowance (2.5 or 5.0 kg of dry matter/d) of autumn pasture (Past), spring pasture silage (Psil), maize silage (Msil), cracked maize grain (Mgr), or palm kernel expeller (PKE), resulting in a total of 11 treatments. Individual cow dry matter intake was determined daily; BW was recorded once per week for cohorts 1 and 2, and 3 times per week for cohorts 3 and 4. The ME contents of feeds were estimated from feed quality assays. Regression analyses were used on each feed to determine the ME requirement for 1 kg of BW gain. The app_kg of Past and Msil was 0.34 and 0.47, respectively; these estimates are in line with published literature. The app_kg of Psil (0.50) was consistent with the published kg for spring pasture, from which the silage was made. Palm kernel expeller had the greatest app_kg (0.61). The reasons for this cannot be deduced from the current study but may reflect the relatively high fat content of the feed and the high kg of fat. The app_kg for Mgr was low (0.38) in comparison with the other supplementary feeds and, in particular, relative to its feed ME and published kg estimates. Although the reason for the low app_kg cannot be deduced from the current data, the most plausible reason is the preferential use of propionate-derived glucose for conceptus metabolism rather than BW gain, a factor not accounted for in previous experimental models that did not use late-gestation cows. In summary, the app_kg for autumn pasture was low but consistent with historical growth rate trials in other ruminant species. In comparison, Msil, Psil, and PKE were used with a greater apparent efficiency (app_kg=0.47 to 0.61), but Mgr resulted in a relatively low rate of gain per MJ of ME (app_kg=0.38). These differences have implications for accurate feed budgeting on farm.

Comparison of updates to the Molly cow model to predict methane production from dairy cows fed pasture.

Molly is a deterministic, mechanistic, dynamic model representing the digestion, metabolism, and production of a dairy cow. This study compared the predictions of enteric methane production from the original version of Molly (MollyOrigin) and 2 new versions of Molly. Updated versions included new ruminal fiber digestive parameters and animal hormonal parameters (Molly84) and a revised version of digestive and ruminal parameters (Molly85), using 3 different ruminal volatile fatty acid (VFA) stoichiometry constructs to describe the VFA pattern and methane (CH4) production (g of CH4/d). The VFA stoichiometry constructs were the original forage and mixed-diet VFA constructs and a new VFA stoichiometry based on a more recent and larger set of data that includes lactate and valerate production, amylolytic and cellulolytic bacteria, as well as protozoal pools. The models' outputs were challenged using data from 16 dairy cattle 26 mo old [standard error of the mean (SEM)=1.7], 82 (SEM=8.7) d in milk, producing 17 (SEM=0.2) kg of milk/d, and fed fresh-cut ryegrass [dry matter intake=12.3 (SEM=0.3) kg of DM/d] in respiration chambers. Mean observed CH4 production was 266±5.6 SEM (g/d). Mean predicted values for CH4 production were 287 and 258 g/d for MollyOrigin without and with the new VFA construct. Model Molly84 predicted 295 and 288 g of CH4/d with and without the new VFA settings. Model Molly85 predicted the same CH4 production (276 g/d) with or without the new VFA construct. The incorporation of the new VFA construct did not consistently reduce the low prediction error across the versions of Molly evaluated in the present study. The improvements in the Molly versions from MollyOrigin to Molly84 to Molly85 resulted in a decrease in mean square prediction error from 8.6 to 8.3 to 4.3% using the forage diet setting. The majority of the mean square prediction error was apportioned to random bias (e.g., 43, 65, and 70% in MollyOrigin, Molly84, and Molly85, respectively, on the forage setting, showing that with the updated versions a greater proportion of error was random). The slope bias was less than 2% in all cases. We concluded that, of the versions of Molly used for pastoral systems, Molly85 has the capability to predict CH4 production from grass-fed dairy cows with the highest accuracy.

Regulation of bovine adipose tissue metabolism during lactation. 7. Metabolism and gene expression as a function of genetic merit and dietary energy intake.

The regulation of adipose tissue metabolism is critical to the efficient establishment and support of lactation, through both energy supply and several endocrine and cytokine factors. We still lack detailed knowledge of the role of transcription and posttranslational regulation of metabolic flux. We need to quantitatively understand the genetic and environmental (primarily dietary) regulation of adipose tissue to help improve productive efficiency. Therefore, objectives of this project were to help define mechanisms of adipose tissue responses to lactation and energy deficit, including changes in gene expression and their relation to changes in metabolic flux and production. A total of 48 cows were selected for genetic merit based on sire predicted transmitting ability of milk. From 21 d prepartum to 60 d in milk (DIM), cows were fed to energy requirements or to 90% of energy requirements, with content of protein, vitamins, and minerals balanced to be the same for both treatments. Adipose tissue biopsies were taken at 21 and 7d prepartum and 7, 28, and 56 DIM to determine rates of lipogenesis and lipolysis, and to measure gene expression of proteins controlling lipolysis. The cows on the restricted diet consumed 12% less feed prepartum and 16% less feed postpartum and dietary energy restriction decreased milk production. The slowest rates of lipogenesis occurred at 7 and 28 DIM; higher-merit cows had faster rates of lipogenesis at 7 DIM but slower rates than lower-merit cows at 28 DIM. Energy restriction decreased lipogenesis. Basal and isoproterenol lipolysis increased with higher milk production and was relatively unaffected by dietary energy intake. The expression of genes controlling lipolysis were not affected by lactation and were slightly increased by dietary restriction, but were not well related to rates of lipolysis. These data confirm and extend previous work that regulation of adipose tissue metabolism in lactation is a function of both diet and genetic merit and is controlled by multiple mechanisms including gene transcription and posttranslational protein modifications.

Change in subcutaneous adipose tissue metabolism and gene network expression during the transition period in dairy cows, including differences due to sire genetic merit.

Adipose metabolism is an essential contributor to the efficiency of milk production, and metabolism is controlled by several mechanisms, including gene expression of critical proteins; therefore, the objective of this study was to determine how lactational state and the genetic merit of dairy cattle affects adipose tissue (AT) metabolism and mRNA expression of genes known to control metabolism. Animals of high (HGM) and low genetic merit (LGM) were fed to requirements, and weekly dry matter intake, milk production, blood glucose, and nonesterified fatty acids were measured. Subcutaneous AT biopsies were collected at -21, 7, 28 and 56 d in milk (DIM). The mRNA expression of genes coding for lipogenic enzymes [phosphoenolpyruvate carboxykinase 1 (soluble) (PCK1), fatty acid synthase (FASN), diacylglycerol O-acyltransferase 2 (DGAT2), and stearoyl-coenzyme A desaturase (SCD)], transcription regulators [peroxisome proliferator-activated receptor γ (PPARG), thyroid hormone responsive (THRSP), wingless-type MMTV integration site family, member 10B (WNT10B), sterol regulatory element binding transcription factor 1 (SREBF1), and adiponectin (ADIPOQ)], lipolytic enzymes [hormone-sensitive lipase (LIPE), patatin-like phospholipase domain containing 2 (PNPLA2), monoglyceride lipase (MGLL), adrenoceptor ß-2 (ADRB2), adipose differentiation-related protein (ADFP), and α-ß-hydrolase domain containing 5 (ABHD5)], and genes controlling the sensing of intracellular energy [phosphodiesterase 3A (PDE3A); PDE3B; protein kinase, AMP-activated, α-1 catalytic subunit (PRKAA1); PRKAA2; and growth hormone receptor (GHR)] was measured. Dry matter intake, blood glucose, and nonesterified fatty acid concentrations did not differ between genetic merit groups. Milk production was greater for HGM cows from 6 to 8 wk postpartum. As expected, the rates of lipogenesis decreased in early lactation, whereas stimulated lipolysis increased. At 7 DIM, lipogenesis in HGM cows increased as a function of substrate availability (0.5, 1, 2, 3, 4, or 8mM acetic acid), whereas the response in LGM cows was much less pronounced. However, the lipogenic response at 28 DIM reversed and rates were greater in tissue from LGM than HGM cows. Peak lipolytic response, regardless of DIM, was observed at the lowest dose of isoproterenol (10(-8)M), and -21 d tissue had a greater lipolysis rate than tissue at 7, 28, and 56 d. In HGM compared with LGM cows, stimulated lipolysis at 7 and 28 DIM was greater but peaked at 10(-7)M isoproterenol, suggesting differences in tissue responsiveness due to genetic merit. Regardless of genetic merit, the expression of lipogenic genes decreased markedly in early lactation, whereas those controlling lipolysis stayed similar or decreased slightly. Cows of HGM had lower expression of lipogenic genes after parturition and through 56 DIM. In contrast, the expression of most of the lipolytic enzymes, receptors and proteins was similar in all cows pre- and postpartum. These results confirm that gene transcription is a major control mechanism for AT lipogenesis during early lactation, but that control of lipolysis is likely primarily by posttranslational mechanisms.

Ruminant Nutrition Symposium: a systems approach to integrating genetics, nutrition, and metabolic efficiency in dairy cattle.

The role of the dairy cow is to help provide high-quality protein and other nutrients for humans. We must select and manage cows with the goal of reaching the greatest possible efficiency for any given environment. We have increased efficiency tremendously over the years, yet the variation in productive and reproductive efficiency among animals is still quite large. In part this is because of a lack of full integration of genetic, nutritional, and reproductive biology into management decisions. However, integration across these disciplines is increasing as biological research findings show more specific control points at which genetics, nutrition, and reproduction interact. An ordered systems biology approach that focuses on why and how cells regulate energy and N use and on how and why organs interact by endocrine and neurocrine mechanisms will speed improvements in efficiency. More sophisticated dairy managers will demand better information to improve the efficiency of their animals. Using genetic improvement and proper animal management to improve milk productive and reproductive efficiency requires a deeper understanding of metabolic processes during the transition period. Using existing metabolic models, we can design experiments specifically to integrate new data from transcriptional arrays into models that describe nutrient use in farm animals. A systems modeling approach can help focus our research to make faster and large advances in efficiency and show directly how this can be applied on the farms.

Co-occurring weight problems among children with attention deficit/hyperactivity disorder: the role of executive functioning.

OBJECTIVE: To explore the link between pediatric obesity and attention deficit/hyperactivity disorder (ADHD) by examining whether executive functioning (EF) and medication status are associated with body mass index (BMI) and weight status in children with ADHD. METHOD: Participants for this study included 80 children (mean age=10 years, 9 months) with a DSM-IV diagnosis of ADHD, confirmed by a comprehensive clinical diagnostic assessment. Children's EF was measured using three neuropsychological tests, and severity of ADHD symptoms and medication status were obtained from parent report. Children's height and weight were also measured during the visit using a wall-mounted stadiometer and a balance beam scale. RESULTS: Children with ADHD who performed poorly on the neuropsychological battery had greater BMI z-scores, and were more likely to be classified as overweight/obese compared with children with ADHD who performed better on the neuropsychological battery. In addition, children with ADHD who were taking a stimulant medication had significantly lower BMI z-scores compared with children with ADHD who were not taking medication or who were taking a non-stimulant medication. CONCLUSION: EF is more impaired among children with ADHD and co-occurring weight problems, highlighting the importance of self-regulation as a link between pediatric obesity and ADHD.

Differential expression of genes in adipose tissue of first-lactation dairy cattle.

Adipose tissue metabolism is an essential factor in establishment of a successful lactation, and we have a good understanding of changes in metabolic flux in relation to lactation, parity, and diet. However, the mechanisms of control of flux are less well understood. To continue our investigations into the control of adipose tissue metabolism, we conducted a transcriptomic analysis of adipose tissue of dairy cattle in late pregnancy and early lactation. Our objective was to determine the changes in gene expression in adipose tissue between 30 d prepartum and 14 d in milk in first-lactation animals, and to determine if changes in expression were related to practical production variables. Animals were Holstein heifers fed the same diet to National Research Council requirements, and adipose tissue was biopsied at 30 d prepartum and 14 DIM. Total RNA was extracted and used to determine gene expression on a bovine gene array. Genes that code for proteins controlling fatty acid transport were highly expressed including fatty acid binding proteins (FABP4 and FABP5) and lipoprotein lipase. Among those genes increasing in expression were those controlling lipolysis, including ADRB2 (52%) and LIPE (23%). Many genes coding for enzymes controlling lipogenesis decreased, including SREBP (-25%), TSHSP14 (-30.8%), LPL (-48.4%), and ACACA (-63.9%). This gene expression array analysis in adipose tissue of lactating dairy cattle identifies several key genes that are components of the adaptation to lactation that can be incorporated into models of nutritional efficiency and may be amenable to genetic or dietary manipulation.

ASAS Centennial Paper: The future of teaching and research in companion animal biology in departments of animal sciences.

Departments of animal sciences must be relevant to a society in which a small number of people can raise almost all the food animal products needed. The declining number of people involved in animal agriculture has decreased enrollment of students interested in food animals in many departments of animal science. However, several departments welcomed students from a diverse background and began research on animals other than food animals. In many states, the undergraduate enrollment is made up primarily of students interested only in companion animals. A benefit of this is that we have recruited new students into animal agriculture and they have gone on to excellent careers. We have a new challenge now: how to maintain and expand the efforts in teaching, research, and outreach of companion animal science. Departments wishing to expand in teaching have examples of successful courses and curricula from other departments. Some departments have expanded their teaching efforts across their own university to teach about pets to a wider audience than their own majors; other departments can follow. In research, a small number of faculty have been able to establish extramurally funded projects on pets, including horses. But it will be difficult for more than a handful of departments to have a serious research effort in dogs, cats, birds, fish, or exotic animals. Departments will have to make a concerted effort to invest in such endeavors; joint ventures with other universities and colleges of veterinary medicine (or medicine) will probably be required. Funding sources for "traditional" efforts in nutrition, reproduction, and physiology are small and inconsistent; however, with the progress of the equine, canine, and feline genome projects, there should be opportunities from federal funding sources aimed at using animal models for human health. In addition, efforts in animal behavior and welfare can be expanded, perhaps with some funding from private foundations or animal-supportive organizations.

Expression of lipolytic genes in the adipose tissue of pregnant and lactating Holstein dairy cattle.

The objective of this study was to determine the expression of beta-adrenergic receptors, hormone-sensitive lipase, and its cofactor perilipin in adipose tissue, and their relationships to rates of lipolysis and body fat use in Holstein dairy cattle during late pregnancy and lactation. Twenty Holstein dairy cattle were grouped by lactation number (1, 2, and 3 or more), and subcutaneous adipose tissue was sampled to measure lipolytic rates and gene expression. The 305-d mature-equivalent yields (305ME) for first, second, and third or higher parity cows were 13,220, 15,659, and 13,890 kg [standard error of the means (SEM) 931]. Milk fat and protein averaged 3.55 and 3.3%, across all parities. Milk production at 30 d in milk (DIM) was 30.7 kg/d (3.4) with 3.6% fat and 2.7% protein; and at 90 DIM was 47.5 kg/d (1.5) with 3.4% fat and 2.9% protein. Body weight and body condition score (BCS), measured at -30, 30, 90, and 270 DIM averaged 697, 605, 652, and 693 kg and 3.3, 2.4, 2.8, and 2.8 BCS units. Adipose tissue was extracted for RNA and tissue was incubated to measure basal and stimulated lipolysis. Basal lipolysis increased following parturition, and basal and stimulated lipolysis peaked at 90 DIM. The B1, B2, and B3 adrenergic receptors (AR) were expressed at all time points, as shown by PCR and agarose gel analysis as well as real-time reverse transcription-PCR. Expression of B1 AR, relative to that at d -30, increased 170, 72, and 112% at 30, 90, and 270 DIM. Expression of B2 AR increased 75, 121, and 100%; and that of B3 AR increased 111, 125, and 69%. Expression of hormone-sensitive lipase increased 180, 359, and 47% at the same time points. Expression of perilipin increased 227, 1,847, and 126%. The greatest expression of these 5 genes corresponded with the fastest rates of lipolysis at 90 DIM. This work demonstrates that an increase in the expression of beta-adrenergic receptors is part of the multifaceted regulation of lipolysis in dairy cattle.

Effects of chromium propionate on response to an intravenous glucose tolerance test in growing Holstein heifers.

To test the effect of chromium propionate on glucose utilization in growing dairy heifers, 0, 5, 10, or 15 mg of chromium/d were fed to 20 Holstein heifers of 11 to 14 mo of age, in a replicated Latin square. A 2-wk adaptation period was followed by 4 periods of 2 wk each with a 2-wk flush out period between treatments. Treatments were allotted to periods in a design balanced for potential carryover effects. Chromium propionate was fed in 0.25 kg/d of ground corn individually. After 14 d on each treatment, animals were fitted with an indwelling jugular catheter, and an intravenous glucose tolerance test was conducted the following morning. Body weights increased throughout the experiment, but weights and condition scores were unaffected by treatment. Chromium supplementation increased basal glucose and decreased basal insulin and nonesterified fatty acids (NEFA) in serum in a dose-dependent, quadratic manner. Chromium increased glucose clearance rate as measured by half-life, time to nadir, and area under the curve. Over all periods, insulin concentrations tended to be lower in treated animals whereas clearance rates were unchanged. Serum NEFA levels were negatively correlated with glucose, such that treated animals with increased glucose had lower NEFA overall. There was an apparent long-term effect of chromium, because heifers in period 4 on the control diet had reduced insulin concentrations than those in the other control periods. Chromium propionate may increase glucose utilization in growing dairy heifers.

Influence of abomasal carbohydrates on subcutaneous, omental, and mesenteric adipose lipogenic and lipolytic rates in growing beef steers.

To determine the response to alteration in site and form of carbohydrate delivery to the digestive tract, in vitro rates of lipogenesis and lipolysis in mesenteric (MESA), omental (OMA), and subcutaneous (SQA) adipose depots were compared. Forty crossbred beef steers (243 +/- 2 kg of BW) were fed 161 (LI) or 214 (HI) kcal of ME/(kg of BW(0.75) x d) or they were fed LI and infused for 35 d into the rumen (R) or abomasum (A) with starch hydrolysate (SH) or into the abomasum with glucose (G). Jugular blood samples were collected, steers were slaughtered, and adipose depots were sampled and prepared for assessment of lipogenesis and lipolysis in vitro. Blood concentrations of glucagon were increased (P = 0.04) in HI-H2O compared with LI-H2O steers, whereas A-SH tended to increase (P = 0.08) circulating IGF-I relative to R-SH, and A-G tended to have elevated (P = 0.09) T3 compared with A-SH. Lipolysis, as assessed by NEFA release, was unaffected by treatment. Glycerol release by the MESA and SQA was increased or tended to be increased (P < or = 0.08) in HI-H2O compared with LI-H2O steers. In A-G compared with A-SH steers, glycerol release from OMA increased (P = 0.008) and from SQA tended to be increased (P = 0.08). Acetate incorporation into total neutral lipids (TNL) increased or tended to increase with ME intake and SH infusion (P < or = 0.09) across all depots. Rates of acetate incorporation into fatty acids (FA) also increased or tended to be increased (P < or = 0.1) by SH infusion across all depots, but only that of SQA was increased with ME intake (HI-H2O vs. LI-H2O; P = 0.02). Rates of acetate incorporation into FA and TNL in MESA were increased (P < or = 0.03) by A-SH compared with R-SH, but site of SH infusion did not affect the rates in SQA or OMA. Glucose incorporation into TNL for MESA and SQA increased or tended to be increased (P < or = 0.1) by dietary and infused energy, whereas for OMA they tended to be increased (P = 0.1) only by SH infusion. In contrast, glucose incorporation into FA was unaffected by energy supply but tended to be increased (P = 0.07) by SH in MESA and tended to be greater (P = 0.08) for A-G than A-SH in OMA. The general across-depot pattern of acetate incorporation rate into FA and TNL was SQA > OMA > MESA, whereas, for glucose incorporation, rates across depots were equivalent. These data provide evidence that the postruminal supply of energy, specifically carbohydrate, stimulates lipogenesis from acetate and glucose and is more pronounced in abdominal depots relative to the subcutaneous depot.

Metabolic models of ruminant metabolism: recent improvements and current status.

The NC-1009 regional research project has two broad goals of quantifying the properties of feeds and the metabolic interactions among nutrients that influence nutrient availability for milk production and that alter synthesis of milk, and using those quantitative relationships to challenge and refine computer-based nutrition systems for dairy cattle. The objective of this paper was to review progress in modeling. Significant progress has been made in model refinements over the past 10 yr as exemplified by the most recent NRC model (2001) and work on the Molly model of Baldwin and colleagues (1987). These models have different objectives but share many properties. The level of aggregation of the NRC model (2001) does not allow detailed analyses of specific metabolic reactions that affect nutritional efficiency. The Baldwin model is aggregated at the pathway level and is therefore amenable to assessment with a broad range of biological measurements. Recent improvements to that model include the addition of an ingredient based input scheme, use of in situ data to set ruminal protein degradation rates, and refinement of the representation of mammary cell numbers and activity. Although the Baldwin model appears to be appropriate structurally, several parameters are known to be inadequate. Predictions of ruminal N metabolism and total-tract starch digestions have similar accuracy as the NRC model. However, the NRC more accurately predicts total-tract fiber digestion and both models significantly overpredict total-tract lipid digestion. These errors contribute to overpredictions of weight retention when simulating full lactations with the Baldwin model and may result in performance prediction errors with the NRC model. Limitations remain in the descriptions of metabolism and metabolic regulation of the splanchnic, viscera, adipose tissue, body muscle, and mammary tissue. Integration of genetic control mechanisms can expand these efforts to assist genetic selection as well as feeding management decisions.

Adipose tissue metabolism and production responses to calcium propionate and chromium propionate.

The objective was to determine action of calcium propionate and chromium propionate on lipogenesis and lipolysis in adipose tissue, dry matter (DM) intake, milk production and composition, and serum glucose and free fatty acids in Holstein dairy cattle treated from 21 d prepartum to 35 d postpartum. Twelve multiparous animals were assigned to each treatment: control (C), calcium propionate (CaP, 0.125 kg/d), chromium propionate (CrP, 10 mg of trivalent Cr/d), and both. All animals were switched to control at 36 days in milk (DIM) and the trial continued to 90 DIM. Biopsies of adipose tissue were taken at -7, 14, 28, and 56 d from calving. Control intake prepartum was 10.6 +/- 2 kg/d. Calcium propionate increased DM intake 11% prepartum and 13% postpartum; CrP increased DM intake 7 and 16%; and the combination treatment had no effect. Milk yield was 44.2 kg/d for controls and 46.8 kg/d for d 1 to 90 for CrP-treated cows. Adipose tissue lipogenesis in cows treated with either CaP or CrP was 1.25 to 78 times as fast as controls from 14 to 56 d and had returned to prepartum rates by 56 d. From 14 to 28 d, basal lipolysis in CaP- or CrP-treated cows ranged from 27 to 102% of control, whereas stimulated lipolysis was 61 to 113% of control. Milk fat yield was 92 to 95% of control on calcium and chromium propionate; the difference was similar to the net reduction in adipose lipolysis. Milk lactose, protein, and solids-not-fat did not differ among treatments. Providing a small amount of gluconeogenic precursors may reduce net lipolysis, allowing increased feed intake and milk production. The effect is thought to be through chromium acting to increase glucose flux into adipocytes.

A semi-empirical molecular orbital scheme to study electron transfer in iron-sulphur proteins.

We describe the use of the semi-empirical molecular orbital method PM3 (parametric method 3) to study the electronic structure of iron-sulphur proteins. We first develop appropriate parameters to describe models of the redox site of rubredoxins, followed by some preliminary calculations of multinuclear iron systems of relevance to hydrogenases.