Daily Injection of the ß2 Adrenergic Agonist Clenbuterol Improved Muscle Glucose Metabolism, Glucose-Stimulated Insulin Secretion, and Hyperlipidemia in Juvenile Lambs Following Heat-Stress-Induced Intrauterine Growth Restriction.

Stress-induced fetal programming diminishes ß2 adrenergic tone, which coincides with intrauterine growth restriction (IUGR) and lifelong metabolic dysfunction. We determined if stimulating ß2 adrenergic activity in IUGR-born lambs would improve metabolic outcomes. IUGR lambs that received daily injections of saline or the ß2 agonist clenbuterol from birth to 60 days were compared with controls from pair-fed thermoneutral pregnancies. As juveniles, IUGR lambs exhibited systemic inflammation and robust metabolic dysfunction, including greater (p < 0.05) circulating TNFα, IL-6, and non-esterified fatty acids, increased (p < 0.05) intramuscular glycogen, reduced (p < 0.05) circulating IGF-1, hindlimb blood flow, glucose-stimulated insulin secretion, and muscle glucose oxidation. Daily clenbuterol fully recovered (p < 0.05) circulating TNFα, IL-6, and non-esterified fatty acids, hindlimb blood flow, muscle glucose oxidation, and intramuscular glycogen. Glucose-stimulated insulin secretion was partially recovered (p < 0.05) in clenbuterol-treated IUGR lambs, but circulating IGF-1 was not improved. Circulating triglycerides and HDL cholesterol were elevated (p < 0.05) in clenbuterol-treated IUGR lambs, despite being normal in untreated IUGR lambs. We conclude that deficient ß2 adrenergic regulation is a primary mechanism for several components of metabolic dysfunction in IUGR-born offspring and thus represents a potential therapeutic target for improving metabolic outcomes. Moreover, benefits from the ß2 agonist were likely complemented by its suppression of IUGR-associated inflammation.

Daily injection of the ß2 adrenergic agonist clenbuterol improved poor muscle growth and body composition in lambs following heat stress-induced intrauterine growth restriction.

Background: Intrauterine growth restriction (IUGR) is associated with reduced ß2 adrenergic sensitivity, which contributes to poor postnatal muscle growth. The objective of this study was to determine if stimulating ß2 adrenergic activity postnatal would rescue deficits in muscle growth, body composition, and indicators of metabolic homeostasis in IUGR offspring. Methods: Time-mated ewes were housed at 40°C from day 40 to 95 of gestation to produce IUGR lambs. From birth, IUGR lambs received daily IM injections of 0.8 µg/kg clenbuterol HCl (IUGR+CLEN; n = 11) or saline placebo (IUGR; n = 12). Placebo-injected controls (n = 13) were born to pair-fed thermoneutral ewes. Biometrics were assessed weekly and body composition was estimated by ultrasound and bioelectrical impedance analysis (BIA). Lambs were necropsied at 60 days of age. Results: Bodyweights were lighter (p ≤ 0.05) for IUGR and IUGR+CLEN lambs than for controls at birth, day 30, and day 60. Average daily gain was less (p ≤ 0.05) for IUGR lambs than controls and was intermediate for IUGR+CLEN lambs. At day 58, BIA-estimated whole-body fat-free mass and ultrasound-estimated loin eye area were less (p ≤ 0.05) for IUGR but not IUGR+CLEN lambs than for controls. At necropsy, loin eye area and flexor digitorum superficialis muscles were smaller (p ≤ 0.05) for IUGR but not IUGR+CLEN lambs than for controls. Longissimus dorsi protein content was less (p ≤ 0.05) and fat-to-protein ratio was greater (p ≤ 0.05) for IUGR but not IUGR+CLEN lambs than for controls. Semitendinosus from IUGR lambs had less (p ≤ 0.05) ß2 adrenoreceptor content, fewer (p ≤ 0.05) proliferating myoblasts, tended to have fewer (p = 0.08) differentiated myoblasts, and had smaller (p ≤ 0.05) muscle fibers than controls. Proliferating myoblasts and fiber size were recovered (p ≤ 0.05) in IUGR+CLEN lambs compared to IUGR lambs, but ß2 adrenoreceptor content and differentiated myoblasts were not recovered. Semitendinosus lipid droplets were smaller (p ≤ 0.05) in size for IUGR lambs than for controls and were further reduced (p ≤ 0.05) in size for IUGR+CLEN lambs. Conclusion: These findings show that clenbuterol improved IUGR deficits in muscle growth and some metabolic parameters even without recovering the deficit in ß2 adrenoreceptor content. We conclude that IUGR muscle remained responsive to ß2 adrenergic stimulation postnatal, which may be a strategic target for improving muscle growth and body composition in IUGR-born offspring.

Effect of protein and glucogenic precursor supplementation on forage digestibility, serum metabolites, energy utilization, and rumen parameters in sheep.

Supplementation of glucogenic precursors in roughage diets may increase production responses due to improved efficiencies of nutrient utilization. Therefore, the objective of this study was to determine the effect of source of supplemental glucogenic potential (GP) on forage digestibility, serum metabolites, energy utilization, and rumen parameters of growing wethers consuming a roughage diet (8.8% crude protein, 71.4% ash-free neutral detergent fiber). Crossbred wethers (49.1 ± 4.7 kg initial BW; n = 16) were utilized in a 4 × 4 replicated Latin Square design with four periods of 21 d. Supplements were designed to supplement increasing amount of GP: 1) no supplementation (CON; 0 g), 2) 40 g of calcium propionate (CAP; 30 g of GP), 3) 70 g of blood meal + 100 g of feather meal (BF; 40 g of GP), or 4) combination of CAP and BF (COMBO; 70 g of GP). Total fecal and urine collection was conducted from days 13-17 to calculate digestibility estimates and urinary losses. An acetate tolerance test was administered on day 17 to determine the effect of GP on acetate clearance. Blood samples were collected on day 19 and were analyzed for serum concentrations of glucose, urea N (SUN), non-esterified fatty acids, and amino acids. Rumen fluid was collected on day 21 to determine supplementation effects on ruminal volatile fatty acid (VFA) and ammonia concentrations. Wethers receiving BF and COMBO supplementation had greatest (P ≤ 0.01) DM and OM total tract digestibility. Supplementation did not affect (P ≥ 0.37) NDF digestibility or digestible energy. Urinary nitrogen excretion was greatest (P = 0.02) for BF and COMBO. Circulating serum essential amino acid concentration was increased (P < 0.01) in BF and COMBO compared to CAP and CON. In addition, BF and COMBO had increased (P < 0.01) SUN concentrations compared to CAP and CON. Acetate half-life was not affected (P = 0.39) by supplementation strategy. However, area under the curve (AUC) for acetate was decreased (P = 0.04) with supplementation of BF and COMBO compared to CON-fed wethers. Ruminal propionate concentration was increased (P ≤ 0.01) for wethers fed CAP and COMBO supplementation, which resulted in decreased (P ≤ 0.01) A:P ratio. Overall, these results indicate that the increased propionate supply by providing propionate salts did not result in a protein sparing impact or increased N retention.

Intermittent maternofetal oxygenation during late gestation improved birthweight, neonatal growth, body symmetry, and muscle metabolism in intrauterine growth-restricted lambs.

In humans and animals, intrauterine growth restriction (IUGR) results from fetal programming responses to poor intrauterine conditions. Chronic fetal hypoxemia elevates circulating catecholamines, which reduces skeletal muscle ß2 adrenoceptor content and contributes to growth and metabolic pathologies in IUGR-born offspring. Our objective was to determine whether intermittent maternofetal oxygenation during late gestation would improve neonatal growth and glucose metabolism in IUGR-born lambs. Pregnant ewes were housed at 40 °C from the 40th to 95th day of gestational age (dGA) to produce IUGR-born lambs (n = 9). A second group of IUGR-born lambs received prenatal O2 supplementation via maternal O2 insufflation (100% humidified O2, 10 L/min) for 8 h/d from dGA 130 to parturition (IUGR+O2, n = 10). Control lambs (n = 15) were from pair-fed thermoneutral ewes. All lambs were weaned at birth, hand-reared, and fitted with hindlimb catheters at day 25. Glucose-stimulated insulin secretion (GSIS) and hindlimb hyperinsulinemic-euglycemic clamp (HEC) studies were performed at days 28 and 29, respectively. At day 30, lambs were euthanized and ex vivo HEC studies were performed on isolated muscle. Without maternofetal oxygenation, IUGR lambs were 40% lighter (P < 0.05) at birth and maintained slower (P < 0.05) growth rates throughout the neonatal period compared with controls. At 30 d of age, IUGR lambs had lighter (P < 0.05) hindlimbs and flexor digitorum superficialis (FDS) muscles. IUGR+O2 lambs exhibited improved (P < 0.05) birthweight, neonatal growth, hindlimb mass, and FDS mass compared with IUGR lambs. Hindlimb insulin-stimulated glucose utilization and oxidation rates were reduced (P < 0.05) in IUGR but not IUGR+O2 lambs. Ex vivo glucose oxidation rates were less (P < 0.05) in muscle from IUGR but not IUGR+O2 lambs. Surprisingly, ß2 adrenoceptor content and insulin responsiveness were reduced (P < 0.05) in muscle from IUGR and IUGR+O2 lambs compared with controls. In addition, GSIS was reduced (P < 0.05) in IUGR lambs and only modestly improved (P < 0.05) in IUGR+O2. Insufflation of O2 also increased (P < 0.05) acidosis and hypercapnia in dams, perhaps due to the use of 100% O2 rather than a gas mixture with a lesser O2 percentage. Nevertheless, these findings show that intermittent maternofetal oxygenation during late gestation improved postnatal growth and metabolic outcomes in IUGR lambs without improving muscle ß2 adrenoceptor content.

Maternofetal inflammation induced for 2 wk in late gestation reduced birth weight and impaired neonatal growth and skeletal muscle glucose metabolism in lambs.

Intrauterine stress impairs growth and metabolism in the fetus and offspring. We recently found that sustained maternofetal inflammation resulted in intrauterine growth-restricted (MI-IUGR) fetuses with asymmetric body composition, impaired muscle glucose metabolism, and ß-cell dysfunction near term. These fetuses also exhibited heightened inflammatory tone, which we postulated was a fetal programming mechanism for the IUGR phenotype. Thus, the objective of this study was to determine whether poor growth and metabolism persisted in MI-IUGR lambs after birth. Polypay ewes received serial lipopolysaccharide or saline injections in the first 2 wk of the third trimester of pregnancy to produce MI-IUGR (n = 13) and control (n = 12) lambs, respectively. Lambs were catheterized at 25 d of age. ß-Cell function was assessed at 29 d, hindlimb glucose metabolism at 30 d, and daily blood parameters from day 26 to 31. Glucose metabolism was also assessed in flexor digitorum superficialis (FDS) muscle isolated at necropsy on day 31. Asymmetric body composition persisted in MI-IUGR neonates, as these lambs were lighter (P < 0.05) than controls at birth and 31 d, but body and cannon bone lengths did not differ at either age. FDS muscles from MI-IUGR lambs were smaller (P < 0.05) and exhibited reduced (P < 0.05) glucose oxidation and Akt phosphorylation but similar glucose uptake compared with controls when incubated in basal or insulin-spiked media. Similarly, hindlimb glucose oxidation was reduced (P < 0.05) in MI-IUGR lambs under basal and hyperinsulinemic conditions, but hindlimb glucose utilization did not differ from controls. Circulating urea nitrogen and cholesterol were reduced (P < 0.05), and triglycerides, high-density lipoprotein cholesterol, and glucose-to-insulin ratios were increased (P < 0.05) in MI-IUGR lambs. Glucose and insulin concentrations did not differ between groups during basal or hyperglycemic conditions. Although circulating monocyte and granulocyte concentrations were greater (P < 0.05) in MI-IUGR lambs, plasma tumor necrosis factor α (TNFα) was reduced (P < 0.05). FDS muscle contained greater (P < 0.05) TNF receptor 1 (TNFR1) and IκBα protein content. These findings indicate that maternofetal inflammation in late pregnancy results in fetal programming that impairs growth capacity, muscle glucose oxidation, and lipid homeostasis in offspring. Inflammatory indicators measured in this study appear to reflect heightened cytokine sensitivity in muscle and compensatory systemic responses to it.

Evaluation of estrous synchronization protocols on ewe reproductive efficiency and profitability.

A 2-year experiment was conducted to determine the effect of a single injection of prostaglandin after initiation of the breeding season on ewe estrous synchronization. Rambouillet ewes (n = 101; Year 1 = 52; Year 2 = 49) assigned to one of three treatments: untreated (CON); 12-d CIDR insert (CIDR); or 1 injection of prostaglandin at d 2.5 (1 PG) after rams were placed with ewes. Rams were placed with ewes at the time of CIDR removal (d 0) and remained with ewes during a 35-d breeding season. Both the CIDR- (94%) and 1 PG (73.5%) treatment groups had a larger number (P ≤ 0.01) of ewes bred in the first 5 d of the breeding season compared to ewes of the control (33%) group. As expected, CIDR-treated ewes had a shorter time to mating, than 1 PG-treated ewes and ewes of the control group had a longer interval to mating than both CIDR- and 1 PG-treated ewes (P ≤ 0.01). The number of lambs born per ewe and kg of lamb weaned per ewe was not different (P ≥ 0.31) among treatment groups. Additionally, there was no difference (P =  0.78) in net profit per ewe among treatment groups. Based on these data, utilizing a single injection of PG 2.5 d after initiation of the breeding season resulted in similar pregnancy rates at d 5 of the breeding season when compared with CIDR-treated ewes indicating the potential utilization of the 1PG protocol in a confinement setting as a viable method for estrous synchronization.

Brangus cows have ovarian reserve parameters more like Brahman than Angus cows.

Bos indicus females have more surface antral follicles than Bos taurus females; however, histological studies demonstrated no difference in total number of primordial follicles between these two biological types of cattle. Primordial follicle density in the ovary was less in Nelore ovaries compared to Angus ovaries, but no studies have examined the primordial follicle density in Bos indicus cross-bred females. It, therefore, was hypothesized that primordial follicle density in the ovary would decrease as percentage Bos indicus increased. Ovaries were collected from cross-bred Angus (n = 32, no Bos indicus influence), Brangus (n = 15), or Brahman (n = 9) cows and prepared for histological evaluation. There was no difference in total number of primordial follicles per ovary between breeds (P > 0.10). When numbers of primordial follicles were expressed on a per gram of ovarian tissue basis, there were fewer primordial follicles per gram of ovarian tissue in Brangus and Brahman cows than in Angus cows (P < 0.05). Brangus cows did not differ from Brahman cows in primordial follicle density (P > 0.10). Differences in primordial follicle density could indicate differences in capacity of ovarian stroma to produce factors necessary for oogonial proliferation and primordial follicle formation among breeds. Identifying these factors could improve the aprroach for culturing pre-antral follicles of cattle. Furthermore, these results explain why ultrasonographic antral follicle counts may need to be adjusted to a greater threshold to predict size of the ovarian reserve and determine ovarian reserve related reproductive traits in Bos indicus females.

The effect of cow udder score on cow/calf performance in the Nebraska Sandhills.

Poor udder and teat confirmation decreases profitability due to decreased calf weaning weight, increased incidence of mastitis and labor, and decreased cow lifetime productivity. Therefore, the objective of this retrospective study was to evaluate the effect of beef cow udder score on cow performance and pre- and postweaning progeny performance. In a 5-yr study, crossbred cows at the Gudmundsen Sandhills Laboratory, Whitman, NE, were assigned an udder score each year at calving, from 1 to 5, using an udder and teat combination score. Cows were grouped by udder scores and classified as either low udder score (LUS, udder score 1 or 2; n = 223) or high udder score (HUS, udder score 3 or 4; n = 1,742). The udder score combines udder conformation and a teat scoring system. Low udder scores consisted of pendulous udders and large teats, whereas HUS consisted of tight udders and small, symmetrical teats. Mixed models were used to evaluate udder score on cow performance and calf pre- and postweaning performance. Cow body weight (BW) at prebreeding and weaning was greater (P < 0.01) in LUS cows compared with HUS counterparts. Pregnancy rate was not different (P = 0.35) between udder classification groups. Calf BW at birth (P = 0.95), weaning (P = 0.40), and adjusted 205-d BW (P = 0.28) were not different between udder groups. Cow udder score did not influence feedlot entry (P = 0.41) and final BW (P = 0.30), dry matter intake (P = 0.53), average daily gain (P = 0.60), and gain:feed ratio (P = 0.85) of steer progeny. However, steers from HUS dams had greater hot carcass weight (HCW; P = 0.04) and backfat thickness (P = 0.02) compared with LUS counterparts. Results from this study suggest cows with less desirable udder structure may not have a negative impact on calf preweaning growth and performance; however, backfat thickness and HCW in the finishing phase were lower in steers from cows with a lower udder score.

The effect of precipitation received during gestation on progeny performance in Bos indicus influenced beef cattle.

The objective of this retrospective study was to determine the effect of precipitation level during key fetal development periods on beef progeny performance. The hypothesis that was precipitation level during different periods of gestation would program subsequent calves for an environment similar to that experienced in utero resulting in altered growth and reproductive performance. Data were collected on Brangus cows (n = 2,429) over a 46-yr span at the Chihuahuan Desert Rangeland Research Center. Recorded precipitation values were used to calculate average precipitation associated with total gestation (April-March), early gestation, (July-September), and late gestation (December-February). These values were used to classify treatments: low (z value ≤ -1.00), average (z value -0.99 to +0.99), and high (z value ≥ +1.00) for each time period. Calves experiencing high precipitation throughout gestation had heavier body weight (BW) at birth (P = 0.02), weaning (P = 0.05), and adjusted 205-d BW (P = 0.04) than those experiencing low precipitation . Female progeny gestated during low precipitation throughout gestation were more likely to remain (P < 0.0001) in the herd and calve after the age of 8 yr when compared to heifers experiencing high precipitation levels in utero (38% vs. 16% ± 5%, respectively). In addition, a greater percentage (P < 0.0001) of heifers experiencing low precipitation levels during the early gestation period produced a calf within the herd after 8 yr of age. Similarly, calves experiencing low precipitation during those same time points also had a greater number of calves while in production (P < 0.0001) when compared to the average and high precipitation groups. These results indicate that selection of heifers exposed to lower than average precipitation levels in utero may result in increased herd retention and productivity.

BEEF SPECIES-RUMINANT NUTRITION CACTUS BEEF SYMPOSIUM: Sustainable and economically viable management options for cow/calf production through enhanced beef cow metabolic efficiency1.

Beef cow herds are expected to be metabolically and reproductively efficient in varied and ever changing environmental conditions. Therefore, selection and management of grazing beef cows provides unique and diverse challenges in achieving optimal production efficiency for any environment. Beef cows face dynamic and highly variable nutritional environments that periodically are inadequate in meeting nutrient and energy requirements. Nutritional management during high metabolically stressed and key physiological states can lead to increased or decreased metabolic efficiency. Conversely, cow metabolic efficiency may be reduced in many production systems due to surplus nutritional inputs and reduced exposure to environmental stressors. Alternatively, metabolically potent supplementation strategies targeting enhanced energy metabolism and endocrine mechanisms would increase beef cow metabolic and economic efficiency. Metabolic efficient beef cows adapt to environmental changes by adjusting their metabolic energy utilization in order to match current environmental conditions and remain reproductively competent. This mechanism involves adaptive processes that drive adjustments in nutrient partitioning and energy utilization efficiency. However, the variation in metabolic and reproductive efficiency among beef cows within cow/calf production systems is substantial, suggesting a lack of complete integration of nutrition, genetics, and reproduction with environmental constraints and conditions. Better integration and understanding of the interactions may lead to advancements in metabolic efficiency of the cowherd. Metabolic flexibility is recognized as an important trait in dairy production but has received little attention thus far in beef cattle. Overall, management and supplementation strategies in cow/calf systems from a mechanistic, targeted nutritional approach during key physiological periods would hasten improvements in metabolic efficiency.