Decreased Plasma Nonesterified Fatty Acids Research Articles

Effects of dietary cation-anion differences at the early stage of transitional period on dry matter intake and plasma Ca metabolism in beef cows

The present study investigated the effects of dietary cation-anion differences (DCADs) on dry matter intake (DMI), nutrient digestibility, body condition score (BCS), body fat, plasma ion metabolism, and relative hormone levels through a perinatal feeding experiment. Eighteen healthy Simmental crossbred cows (Simmental ♂ × native Yunnan Yellow ♀; body weight, 325.4 ± 27.63 kg) were allocated to one of three treatment groups with six replicates each. The control (CON) group received basal diet without anionic salt supplementation, with a DCAD of 127.56 mEq kg−1 DM. The T2% and T4% groups received basal diet supplemented with 2% and 4% anionic salts, with DCADs of −1.60 and −129.10 mEq kg−1 DM, respectively. All groups received isoenergetic and isonitrogenous diets. Blood samples were collected on prepartum days 7 and 3; on the day of calving; and on postpartum days 1, 3, 7, 14, and 42. Prenatal urine pH decreased with decreasing DCAD (P < 0.001). Compared with that in the CON group, DMI in the T2% and T4% groups was decreased by respectively 11.4 % and 17.8 % (P = 0.005) at the early stages of perinatal period (−21 to 0 days), but DMI in the T2% group was increased by 9.4 % (P < 0.046) at the later stages of perinatal period (0–21 days). The postpartum BCS in the T2% and T4% groups was 25 % lower than that in the CON group (P = 0.038). Prepartum apparent P digestibility was increased in the T2% and T4% groups (P = 0.017) and prepartum apparent Ca digestibility was increased in the T2% group (P = 0.022). The content of colostrum fat, Ca, lactose, and immunoglobulin G was increased in the T2% group (P < 0.05). On postpartum day 1, the plasma ionized (i) Ca concentrations were increased by 20.4 % and 19.4 % (P < 0.05), the plasma 1,25(OH)2D3 concentrations were increased by 15.6 % and 12.7 % (P < 0.05), and the plasma iK concentrations were decreased by 8.8 % and 9.8 % (P = 0.003) in the T2% and T4% groups, respectively, compared with values in the CON group. In addition, the iMg, iP, and parathyroid hormone levels in the T2% group were increased (P < 0.05). On prepartum day 7, the plasma glucose concentration in the T2% group was higher than that in the CON group (P = 0.010), and on the day of calving, the plasma glucose concentration in the T4% group was higher than that in the T2% group (P = 0.041). On postpartum day 1, the plasma non-esterified fatty acid (NEFA) concentration in the T2% group was lower than that in the CON group (P = 0.021), but there was no significant difference in this concentration between the T4% and CON groups (P > 0.05). The postpartum plasma β-hydroxybutyric acid (BHB) concentrations in the T2% and T4% groups were lower than those in the CON group (P < 0.001). On postpartum day 42, progesterone levels in the T2% and T4% groups were respectively 27.3 % and 16.7 % lower than those in the CON group (P < 0.001). Therefore, the addition of anionic salts to reduce DCAD accelerated the recovery of postpartum DMI, decreased plasma NEFA and BHB concentrations, and increased plasma iCa concentration. Under the present experimental conditions, 2% anionic salt supplementation was more appropriate.

Effect of preshipment preconditioning and injectable antioxidant trace elements (Cu, Mn, Se, Zn) and vitamins (A, E) on plasma metabolite and hormone concentrations and growth in weaned beef cattle.

Weaning and transport represent a high stress time for calves. Preconditioning (PC) by weaning before the transport separate these stressors. The stressors generate oxidative stress, which can be reduced by mineral and vitamin supplementation (MVS) with an antioxidant capacity. Our objective was to evaluate the effect of PC and MVS on performance of steers. The experiment used a 2 × 2 factorial arrangement design, considering a 26-d PC treatment from weaning to transport to the feedlot (day 0), and injectable MVS on days −45, −26, and 0. The MVS consisted of Cu, Zn, Mn, Se, vitamin E (0.2, 0.8, 0.2, 0.1, and 1 mg/kg body weight [BW], respectively), and vitamin A (1,190 IU/kg). Sixty Angus-crossbred steers (186.4 ± 27.6 kg) were randomly assigned to the four treatments (MVS+PC; N+PC; MVS+N; N+N; n = 15 per treatment). BW was recorded on days −45, −26, 0, 8, 15, and 29. On day 0, an additional BW was taken 30 min after the 5-h transportation (day 0.5). Between days 0 and 29, dry matter intake (DMI) and average daily gain (ADG) to DMI ratio (G:F) were measured. Between days −26 and 29 plasma concentrations of glucose, nonesterified fatty acids (NEFA), cortisol, insulin, total antioxidant status (TAS), and thiobarbituric acid-reactive substances were evaluated. Data were analyzed using the MIXED procedure of SAS with repeated measures, using treatment, time, and treatment × time as fixed effects and steer as a random effect. Between days −26 and 0, there was an interaction of MVS × PC (P ˂ 0.01) for ADG. From days −26 to 0, N+N and N+PC had the greatest and lesser ADG, respectively. On day 0.5, no-PC steers tended to lose BW, whereas the PC steers tended to gain BW (P = 0.09). In the period days 0 to 8, there were no differences (P ≥ 0.27) in DMI, but the PC steers had greater G:F and ADG (P < 0.01) compared with no-PC steers. Plasma NEFA concentration on day 0 was affected by MVS × PC (P < 0.01) because MVS decreased plasma NEFA concentration in no-PC steers, but it increased in the PC steers. Plasma concentrations of glucose, insulin, and cortisol did not differ among treatments (P ≥ 0.23). There was an MVS × PC interaction (P = 0.09) for TAS on day 0; N+N had the greatest TAS concentrations and MVS+N had the lowest TAS concentrations. In conclusion, a 26-d PC decreased steers BW compared with no-PC steers. The BW loss during PC was not recovered 29 d after feedlot entry. Despite this BW loss, MVS treatment decreased BW loss in the steers allocated to PC treatment on the day of transport.

Temporal effects of ruminal infusion of propionic acid on hepatic metabolism in cows in the postpartum period

A faster rate of infusion of propionic acid into the rumen of cows in the postpartum period increased meal size compared with a slower rate of infusion in a previous experiment. Because propionate is anaplerotic and stimulates oxidation of acetyl coenzyme A (CoA) in the liver, and hepatic oxidation has been linked to satiety, this result was opposite to our expected response. We then hypothesized that the faster rate of infusion might have saturated the pathway for propionate metabolism in hepatocytes resulting in lower first-pass extraction by the liver. Because we were measuring feeding behavior, we could not sample blood and liver tissue over time in that experiment. Therefore, to determine the temporal effects of propionic acid (PA) infusion on hepatic metabolism and plasma metabolites over the time course of a meal, we infused 1.25 mol of PA (2.5 L of 0.5M PA) over 5 min (FST) or 15 min (SLW) into the rumen. We evaluated response to PA infusions both before feeding, when ruminal PA production by rumen microbes is lower and hepatic acetyl CoA concentration is greater, and 4 h after feeding, when PA production is greater and hepatic acetyl CoA concentration is lower. Blood and liver samples were collected before, and after 5, 15, and 30 min of infusion. Contrary to our hypothesis, the rate of PA infusion into the rumen did not affect plasma propionate concentration, indicating the FST effects on feeding behavior were not because of a limitation on propionate uptake by the liver. However, FST increased plasma glucose and insulin concentrations faster than SLW, resulting in a reduction in plasma nonesterified fatty acid concentration during the time frame of meals. Decreased plasma nonesterified fatty acid concentration during infusion likely decreased the supply of acetyl CoA for oxidation in the liver. The FST treatment also increased fumarate concentration at 5 min after the initiation of infusion but did not affect oxaloacetate concentration compared with SLW, consistent with a limitation to propionate metabolism at that reaction. A metabolic bottleneck at the malate dehydrogenase reaction for FST compared with SLW would further contribute to a reduction in hepatic oxidation within the time frame of a meal, allowing greater meal size, consistent with the hepatic oxidation theory and our previous results.

Hepatic metabolism of propionate relative to meals for cows in the postpartum period

The objective of this research was to identify potential short-term metabolic bottlenecks of propionate metabolism in the liver of dairy cows in the postpartum (PP) period and how such bottlenecks are affected by feeding status. Propionate, produced primarily from the fermentation of starch, decreases dry matter intake for cows in the postpartum period, likely by stimulating oxidation of acetyl-CoA in the liver. In this study, 8 dairy cows [2 blocks of 4 cows each, 6.63 ± 1.19 (mean ± SD) days PP; body condition score of 2.84 ± 0.39] were administered a pulse dose of either 1.5 mol/500 mL of propionic acid (PA) or 500 mL of water (control; CON) to the rumen either 1 h before or 2 h after feeding in a 4 × 4 Latin square design with a 2 × 2 factorial arrangement of treatments. Liver tissue was sampled at -1, 10 and 20 min relative to dosing, and blood was sampled at -30, -20, -10, -1, 5, 10, 15, 20, 25, 30, and 60 min relative to dosing. We hypothesized that rapid propionate absorption results in bottlenecks as enzymes become saturated and cofactors require regeneration. The PA treatment increased plasma propionate and insulin concentrations rapidly, with peaks reached by 5 min regardless of feeding status and cleared from the plasma within 30 min of dosing. The PA treatment decreased plasma nonesterified fatty acid concentration over 30 min compared with CON before but not after feeding. The PA treatment decreased plasma β-hydroxybutyrate concentration and increased plasma lactate concentration compared with CON both before and after feeding. The PA treatment also increased hepatic pyruvate and lactate concentrations compared with CON. The PA treatment tended to increase hepatic isocitrate and fumarate concentrations but did not affect hepatic malate and oxaloacetate concentrations, suggesting that elevated mitochondrial NADH/NAD+ may have slowed the isocitrate dehydrogenase and fumarase reactions. The PA treatment also increased succinate concentration compared with CON, suggesting that a bottleneck may be present at succinate dehydrogenase. The PA treatment tended to increase citrate concentration despite having no effects on acetyl-CoA or oxaloacetate concentrations. These results are in agreement with our hypothesis that rapid absorption of propionate from the rumen and extraction by the liver results in metabolic bottlenecks in the liver that may affect feeding behavior and dry matter intake in dairy cows in the PP period.

Effects of feeding Aspergillus oryzae fermentation product to transition Holstein cows on performance and health

Two experiments examined the effects of Aspergillus oryzae fermentation product (AO; Amaferm®; BioZyme Inc., St. Joseph, MO, USA) on productive variables in transition dairy cows. In experiment 1, 33 Holstein cows (22 multiparous and 11 primiparous) were enrolled from −21 to 60 days in milk (DIM). Cows were individually fed either a control total mixed ration (TMR) diet consisting of primarily alfalfa hay and steam-flaked corn [62:38 and 59:41, forage:concentrate (F:C) for prepartum and postpartum phases, respectively] or the control diet along with 15 g d−1 of AO. In experiment 2, 455 multiparous Holstein cows were enrolled from −21 to 121 DIM. Cows were group-fed either a control TMR diet (n = 228) consisting primarily of corn silage and rolled corn (44:56, F:C) or the control diet (n = 227) with 15 g d−1 of AO. In experiment 1, cows fed AO had increased (P &lt; 0.05) milk production compared with controls (37.7 vs. 34.6 kg d−1). Milk composition, dry matter intake, body weight (BW), and BW loss both prepartum and postpartum did not differ (P &gt; 0.10) between treatments. Cows fed AO tended to have decreased plasma nonesterified fatty acids levels (14%, P &lt; 0.10), but plasma glucose concentration did not differ (P = 0.89). In experiment 2, cows fed AO had decreased milk yield (43.0 vs. 43.8; P &lt; 0.05), and increased milk fat content (3.50% vs. 3.38%; P &lt; 0.01) but similar quantities of 3.5% fat-corrected milk (42.5 vs. 42.7 kg d−1; P &gt; 0.10). Results suggest that AO has the potential to improve aspects of milk production efficiency, but the percentage and types of forage utilized may influence the response.

Solvent-extracted soybean meal top-dressed on a fresh cow diet increased milk production, but not milk components, and decreased plasma non-esterified fatty acids

Post-ruminally infused casein has increased milk and milk protein yield in post-partum cows. We theorised top dressing (TD) higher amounts of soybean meal (SBM) might mimic these effects. Fifty-one multiparous Holstein cows 1 day after calving were assigned to 3 dietary treatments: a base total mixed ration (CON) with 196 g/kg crude protein and 329 g/kg neutral detergent fibre; 17 cows TD with l kg of SBM (SBM1); and 17 cows TD with 2 kg of SBM (SBM2) for 30 days. Milk and milk components were measured at days 9, 18, and 27. Rumen and urine samples were collected on day 27; blood samples were obtained on day 30. Statistical inference was by JMP software (Version 10.0.2, 2012) with production variables analysed as a repeated measures design. Cows fed SBM increased milk yield (P = 0.02; 35.4, 36.6, and 42.6 kg/day for CON, SBM1, and SBM2, respectively). Yield of milk true protein was not different among treatments. Cows fed SBM had lower serum non esterified fatty acids concentrations at day 30 (1.35, 1.13, and 0.59 mM/l; P &amp;lt; 0.01). We conclude that SBM TD beginning immediately after calving may increase milk yield rapidly and decrease dependence on fatty acids for energy.

Effects of TNF receptor blockade on in vitro cell survival and response to negative energy balance in dairy cattle

BackgroundAssociative data and some controlled studies suggest that the inflammatory cytokine tumor necrosis factor (TNF) α can induce fatty liver in dairy cattle. However, research demonstrating that TNFα is a necessary component in the etiology of bovine fatty liver is lacking. The aim of this work was to evaluate whether blocking TNFα signaling with a synthetic cyclic peptide (TNF receptor loop peptide; TRLP) would improve liver metabolic function and reduce triglyceride accumulation during feed restriction.ResultsCapability of TRLP to inhibit TNFα signaling was confirmed on primary bovine hepatocytes treated with recombinant bovine TNFα and 4 doses of TRLP (0, 1, 10, 50 μmol/L) over 24 h. Next, 4 lactating Holstein cows (parity 1.4 ± 0.5, 433 ± 131 d in milk) in an incomplete Latin rectangle design (3 × 2) were subcutaneously administered with different TRLP doses (0, 1.5, 3.0 mg/kg BW) every 4 h for 24 h, followed by an intravenous injection of TNFα (5 μg/kg BW). Before and for 2 h after TNFα injection, TRLP decreased plasma non-esterified fatty acid (NEFA) concentration (P ≤ 0.05), suggesting an altered metabolic response to inflammation. Finally, 10 non-pregnant, non-lactating Holstein cows (3.9 ± 1.1 yr of age) were randomly assigned to treatments: control (carrier: 57% DMSO in PBS) or TRLP (1.75 mg TRLP /kg BW per day). Treatments were administrated every 4 h for 7 d by subcutaneous injection to feed-restricted cows fed 30% of maintenance energy requirements. Daily blood samples were analyzed for glucose, insulin, β-hydroxybutyrate, NEFA, and haptoglobin concentrations, with no treatment effects detected. On d 7, cows completed a glucose tolerance test (GTT) by i.v. administration of a dextrose bolus (300 mg glucose/kg BW). Glucose, insulin, and NEFA responses failed to demonstrate any significant effect of treatment during the GTT. However, plasma and liver analyses were not indicative of dramatic lipolysis or hepatic lipidosis, suggesting that the feed restriction protocol failed to induce the metabolic state of interest. Injection site inflammation, assessed by a scorer blinded to treatment, was enhanced by TRLP compared to control.ConclusionsAlthough the TRLP inhibited bovine TNFα signaling and altered responses to i.v. administration of TNFα, repeated use over 7 d caused apparent local allergic responses and it failed to alter metabolism during a feed restriction-induced negative energy balance. Although responses to feed restriction seemed atypical in this study, side effects of TRLP argue against its future use as a tool for investigating the role of inflammation in metabolic impacts of negative energy balance.

Effects of abomasal infusion of nicotinic acid on responses to glucose and β-agonist challenges in underfed lactating cows

The objectives were to assess the use of nicotinic acid (NA) to chronically (i.e., 74 h) manipulate plasma nonesterified fatty acid (NEFA) concentrations in partially feed-restricted lactating cows, determine whether the reduction of plasma NEFA altered responses to i.v. glucose tolerance test (ivGTT) and whether NA would attenuate an acute lipolytic stimuli of a β-agonist challenge (ivBAC). Eight lactating dairy cows [244±31 d in milk; 696±63kg of body weight (BW)] were blocked by breed and body condition score (3.2±0.4) and randomly assigned to a sequence of 2 treatments in a crossover design. Treatments were 74-h continuous abomasal infusion of NA solution (3mg/h per kg of BW) as an antilipolytic agent to decrease plasma NEFA concentrations or the same volume of water (200mL/h), concomitant with partial feed restriction. From 0 to 74 h of each experimental period, cows were feed-restricted to 33% of the ad libitum intake recorded during the prior 5 d. An ivGTT (0.25g/kg of BW of glucose i.v.) and an ivBAC (4 nmol/kg of BW of isoproterenol hydrochloride, i.v.) were performed at 48 and 72 h, respectively. Intake was 24.1, 8.2, 8.0, and 8.0kg of dry matter/d before restriction, on d 1, 2 and 3, respectively. Nicotinic acid decreased plasma NEFA and increased insulin and glucose concentrations during feed restriction. Nicotinic acid also led to greater glucose and insulin response areas under the curve during ivGTT [glucose: 6,562 vs. 5,056 (mg/dL)×180 min; insulin: 6,042 vs. 2,502 (µIU/mL)×180 min] and ivBAC [glucose: 535 vs. 240 (mg/dL)×120 min; insulin: 1,283 vs. 222 (µIU/mL)×120 min], and enhanced NEFA area under the curve during ivBAC [45,521 vs. 22,862 (µEq/L)×120 min]. Milk, fat, and protein yields (29.1, 1.2, and 0.93kg on d −2, respectively) decreased to 17.9, 0.81, and 0.56kg for control, and 11.5, 0.54, and 0.39kg for NA on d 3, respectively. Nicotinic acid may have decreased production by inhibiting the supply of NEFA for energy and milk fat synthesis. Milk urea nitrogen was increased by NA on d 2 (12.8 vs. 19.1mg/dL) and d 3 (11.6 vs. 17.8mg/dL), probably due to a greater reliance on mobilized amino acids. Somatic cell count was increased by NA on d 3 (187 vs. 848 ×1,000 cells/mL). Patterns of glucose and insulin concentration observed during 74 h of NA infusion reflect a state of insulin resistance, which contrasts with shorter-term responses in nonlactating cows. Data suggest that long-term supraphysiological infusion of NA affected intermediary metabolism beyond antilipolysis and did not inhibit acute lipolytic stimuli of ivBAC.

Differential impacts of high fat and high Se diets on tissue lipid profiles of young adult and old wild‐type and GPX1‐/‐ mice (374.5)

Our previous research has demonstrated hyperinsulinemia and elevated lipogenesis by feeding pigs and rats with Se at 3.0 mg/kg of diet. This study was to determine the impacts of a moderately high Se (1.0 vs. 0.3 mg/kg as selenite) and(or) high fat (60 vs. 16% energy from fat) on lipid profiles in plasma, adipose and liver tissues of young adult (2‐4 mo of age) and old (6‐10 mo of age) wild‐type (WT) and GPX1‐/‐ (KO) male mice. A total of 80 mice were divided into 4 parallel (genotype by age) experiments (n = 5/group) and fed one of 4 diets for 6 wk. Body weight was elevated (P &lt; 0.05) by the high fat diet in old WT and young KO mice, but decreased by high Se diet (P &lt; 0.05) in young WT mice. Both high fat and Se intakes enhanced (P &lt; 0.05) plasma glucose concentrations in old WT mice. High Se intake decreased plasma non‐esterified fatty acids (NEFA) concentrations in young WT mice. There was little effect of high fat or Se intake on plasma lipid profiles of KO mice. Adipose tissue concentrations of triglycerides, cholesterol, and NEFA were consistently elevated by high fat and Se in both young WT and KO mice. In comparison, such effects of the dietary treatments on adipose tissue of old WT and KO mice or on liver of all 4 groups of mice were less obvious or consistent. In conclusion, our results revealed a uniquely high response of adipose tissue lipid profile to dietary intakes of high fat and Se and a strong interaction of age by GPX1 knockout on the response (NIH DK 53018).Grant Funding Source: (NIH DK 53018).

Effect of saturated fatty acid supplementation on production and metabolism indices in heat-stressed mid-lactation dairy cows

Experimental objectives were to determine the effects of supplemental saturated fatty acids on production, body temperature indices, and some aspects of metabolism in mid-lactation dairy cows experiencing heat stress. Forty-eight heat-stressed Holstein cows were allocated into 3 groups (n=16/group) according to a completely randomized block design. Three treatment diets consisted of supplemental saturated fatty acids (SFA) at 0 (SFA0), 1.5 (SFA1.5), or 3.0% (SFA3) of dry matter (DM) for 10 wk. Diets were isonitrogenous (crude protein=16.8%) and contained 1.42, 1.46, and 1.49 Mcal of net energy for lactation/kg of DM for the SFA0, SFA1.5 and SFA3 diets, respectively. The average temperature-humidity index at 0700, 1400 and 2200h was 72.2, 84.3, and 76.6, respectively. Rectal temperatures at 1400h were decreased with fat supplementation. Treatment did not affect dry matter intake (20.1±0.02kg/d), body condition score (2.72±0.04), body weight (627±16.1kg), or calculated energy balance (1.32±0.83Mcal/d). Saturated fatty acid supplementation increased milk yield, milk fat content, and total milk solids. Increasing fat supplementation decreased plasma nonesterified fatty acids (8%) but had no effect on other energetic metabolites or hormones. In summary, supplemental SFA improved milk yield and milk fat content and yield and reduced peak rectal temperatures in mid-lactation heat-stressed dairy cows. This demonstrates the remarkable amount of metabolic heat that is “saved” by energetically replacing fermentable carbohydrates with supplemental SFA.

Chronic metabolic responses of postpartal dairy cows to subcutaneous glucagon injections, oral glycerol, or both

We examined the long-term effects of daily subcutaneous injections of 15mg of glucagon during the first 14 d postpartum with or without coadministration of 400mL of pure glycerol orally on blood metabolites and hormones and liver composition of Holstein dairy cows during early lactation. Fourteen multiparous cows with body condition score of ≥3.5 points (1–5 point scale) were assigned randomly to one of 4 treatment groups—saline, glucagon, glycerol, or glucagon plus glycerol. Fatty liver syndrome was induced by feeding cows a dry-cow ration supplemented with 6kg of cracked corn daily during the last 6 wk of the dry period. Compared with saline treatment (n=3), coadministration of glucagon and glycerol (n=4) increased plasma glucose and insulin and decreased plasma nonesterified fatty acid concentrations in both treatment weeks, whereas glucagon alone (n=3) produced similar changes plus a decrease in plasma β-hydroxybutyrate in the second week only. No significant changes were observed for the glycerol alone treatment (n=4). We conclude that a single daily dose of glycerol for the first 14 d postpartum may potentiate the action of glucagon in the first treatment days to alleviate some symptoms of fatty liver syndrome, such as the increase in plasma nonesterified fatty acids and the decrease in plasma glucose and insulin, in Holstein dairy cows after parturition.

Acute Metabolic Responses of Postpartal Dairy Cows to Subcutaneous Glucagon Injections, Oral Glycerol, or Both

This study examined the effects of multiple subcutaneous glucagon injections with or without co-administration of oral glycerol on energy status-related blood metabolites and hormones of Holstein dairy cows in the first 2 wk postpartum. Twenty multiparous cows were fed a dry cow ration supplemented with 6kg of cracked corn during the dry period to increase the likelihood of developing postpartal fatty liver syndrome. Cows with a body condition score of ≥3.5 points (1- to 5-point scale) were assigned randomly to 1 of 4 treatment groups: saline, glucagon, glycerol, or glucagon plus glycerol. Following treatment, serial blood samples were collected over an 8-h period to determine the effects of glucagon and glycerol on blood metabolites and hormones. Treatment effects were determined by comparing the concentrations of metabolites and hormones during the first 4-h period and the entire 8-h period after treatment administration (time 0) with the concentration of the same compounds at time 0 on d 1, 7, and 13 postpartum. Administration of glucagon alone increased concentrations of plasma glucagon and insulin on d 1, 7, and 13 and increased plasma glucose and decreased plasma nonesterified fatty acids (NEFA) on d 7 and 13 postpartum relative to the saline group. Administration of glycerol alone increased plasma glucose on d 7 and plasma triacylglycerols on d 1 postpartum. Glycerol administration also decreased plasma glucagon and NEFA on d 1, 7, and 13 and plasma β-hydroxybutyrate (BHBA) on d 1 postpartum relative to the saline group. Administration of glucagon plus glycerol increased and sustained concentrations of plasma glucagon, glucose, and insulin on d 1, 7, and 13 and decreased plasma NEFA on d 1, 7, and 13 and BHBA on d 1 and 7. Early postpartal treatment of dairy cows with glucagon plus glycerol increased plasma glucose and insulin, decreased plasma NEFA and BHBA, and increased secretion of liver NEFA as plasma triacylglycerols. This suggests that glucagon and glycerol, when co-administered, act to decrease the likelihood of metabolism-related syndrome development in dairy cows.

Reduction of Plasma NEFA Concentration by Nicotinic Acid Enhances the Response to Insulin in Feed-Restricted Holstein Cows

The objective was to investigate the relationship between elevated plasma nonesterified fatty acid (NEFA) concentration and insulin resistance in Holstein cows. Six nonlactating, nongestating, ruminally cannulated Holstein cows were blocked by body condition score and randomly assigned to a sequence of 2 treatments in a crossover design. Cows were offered legume and grass hay ad libitum supplemented with minerals and vitamins and were allowed free access to water and a trace mineralized salt block. Mobilization of body reserves was stimulated by withdrawing forage for 48h before initiation of treatments. Treatments consisted of 11 hourly abomasal infusions of water (control) or nicotinic acid (NA; 6 mg/h per kg of body weight) as an antilipolytic agent. Infusions of NA decreased plasma NEFA concentration from 545μEq/L to approximately 100μEq/L within 2h after initiation of treatments, and differences were maintained throughout infusions. Intravenous glucose tolerance test was performed 8h after initiation of treatments and was followed by 3h of blood sampling. The reduction of plasma NEFA concentration led to significantly greater glucose clearance rate (1.9 vs. 1.2%/min) and to decreased glucose half-life (37 vs. 58min), time to reach basal concentration (81 vs. 114min) and glucose response area under the curve during 180min of sampling [6,942 vs. 10,085 (μIU/mL)×180 min]. Enhanced glucose clearance was achieved when plasma NEFA was reduced by NA, despite lower insulin concentration (70.0 vs. 97.9±13.4μIU/mL) and a tendency for smaller insulin response area under the curve during 180min of sampling [7,646 vs. 12,104±2,587 (μIU/mL)×180 min], reflecting an increased response to endogenous insulin. Based on literature, we do not expect NA to have altered glucose metabolism directly; therefore, this experiment demonstrates a cause and effect relationship between elevated NEFA and insulin resistance in Holstein cows.

Effect of Glucogenic vs. Lipogenic Diets on Energy Balance, Blood Metabolites, and Reproduction in Primiparous and Multiparous Dairy Cows in Early Lactation

Increasing the availability of glucogenic nutrients relative to lipogenic nutrients has been hypothesized to decrease the production of milk fat, to improve the energy balance (EB), and to decrease the incidence and severity of metabolic and reproductive disorders in dairy cows in early lactation. Therefore, our objective was to evaluate the effects of a glucogenic, lipogenic, or mixed diet on EB, plasma metabolites and metabolic hormones, liver triacylglycerides (TAG), and reproductive variables in high-producing dairy cows in early lactation. Cows (n=114) were randomly assigned to 1 of 3 diets and were fed either a mainly lipogenic diet, a mainly glucogenic diet, or a mixture of both diets (50:50 dry matter basis) from wk 3 before the expected calving date until 9 wk postpartum. Diets were isocaloric (net energy basis) and equal in intestinal digestible protein. Dry matter intake, net energy intake, milk yield, and milk protein percentage did not differ among diets. Milk lactose percentage was less for cows fed the lipogenic diet. Milk fat percentage was less for multiparous cows fed the glucogenic diet compared with cows fed the mixed or lipogenic diet (3.69 vs. 4.02 vs. 4.22±0.07%, respectively). The calculated EB was less negative for multiparous cows fed the glucogenic diet compared with cows fed the mixed or lipogenic diet [−33 vs. −125 vs. −89±21 kJ/(kg0.75 · d), respectively]. Postpartum, the glucogenic diet decreased plasma nonesterified fatty acids, β-hydroxybutyrate, and liver TAG concentrations and increased insulin concentration in multiparous cows. The glucogenic diet tended to decrease the number of days until first milk progesterone rise in multiparous cows compared with the mixed or lipogenic diet (20.4 vs. 24.4 vs. 26.4±2.1 d, respectively). Diet had no effect on any of the above-mentioned variables in primiparous cows, except that milk lactose percentage was greater for primiparous cows fed the glucogenic diet. We concluded that the glucogenic diet was effective in improving the calculated EB and decreasing plasma β-hydroxybutyrate and liver TAG concentrations, suggesting a reduced risk of metabolic disorders in multiparous dairy cows fed a glucogenic diet.

Prevention of Fatty Liver in Transition Dairy Cows by Subcutaneous Injections of Glucagon

The main objective of this study was to test the extent to which injecting glucagon subcutaneously for 14 d beginning at d 2 postpartum would prevent fatty liver development in transition dairy cows. Twenty-four multiparous Holstein cows were fed 6kg of cracked corn in addition to their standard diet during the last 30 d of a dry period to induce postpartum development of fatty liver. Glucagon at either 7.5 or 15mg/d or saline (control) was injected subcutaneously 3 times daily for 14 d beginning at d 2 postpartum. Glucagon at 15mg/d prevented liver triacylglycerol accumulation in postpartum dairy cows. Glucagon at 7.5mg/d showed potential for fatty liver prevention. Glucagon increased concentration of plasma glucose and insulin and decreased plasma nonesterified fatty acid concentrations. No effects of glucagon were detected on plasma β-hydroxybutyrate concentrations. Glucagon affected neither feed intake nor milk production. Moreover, milk composition was not altered by glucagon. Milk urea N concentrations decreased, and plasma urea N concentrations tended to decrease during glucagon administration, indicating that glucagon may improve protein use. Liver glycogen concentrations were not affected by glucagon. No significant differences in body condition scores were detected among treatments throughout the study. These results indicate that subcutaneous glucagon injections can prevent fatty liver in transition dairy cows without causing major production and metabolite disturbances.

Effects of a longitudinal training program on responses to exercise in overweight men.

The aim of this study was to determine how training modifies metabolic responses and lipid oxidation in overweight young male subjects. Eleven overweight subjects were selected for a 4-month endurance training program. Before and after the training period, they cycled for 60 minutes at 50% of their VO(2)max after an overnight fast or 3 hours after eating a standardized meal. Various metabolic and endocrine parameters, and respiratory exchange ratio values were evaluated. Exercise-induced plasma norepinephrine concentration increases were similar before and after training in fasted or fed conditions. After food intake, exercise promoted a decrease in plasma glucose and a higher increase in epinephrine than in fasting conditions. The increase in epinephrine after the meal was more marked after training (264 +/- 32 vs. 195 +/- 35 pg/mL). Training lowered the resting plasma nonesterified fatty acids. During exercise, changes in glycerol were similar to those found before training. Lipid oxidation during exercise was higher in fasting than in fed conditions (15.5 +/- 1.4 vs. 22.3 +/- 1.7 g/h). Training did not significantly increase fat oxidation when exercise was performed in fed conditions, but it did in fasting conditions (18.6 +/- 1.4 vs. 27.2 +/- 1.8 g/h). Endurance training decreased plasma nonesterified fatty acids, cholesterol, and insulin concentrations. Training increased lipid oxidation during exercise, in fasting conditions, and not when exercise was performed after the meal. During exercise in overweight subjects, the fasting condition seems more suited to oxidizing fat and maintaining glucose homeostasis than a 3-hour wait after a standard meal.

Atorvastatin treatment induced peroxisome proliferator-activated receptor α rexpression and decreased plasma nonesterified fatty acids and liver triglyceride in fructose-fed rats

Atorvastatin treatment induced peroxisome proliferator-activated receptor α rexpression and decreased plasma nonesterified fatty acids and liver triglyceride in fructose-fed rats

Hormone-sensitive Lipase Deficiency in Mice Changes the Plasma Lipid Profile by Affecting the Tissue-specific Expression Pattern of Lipoprotein Lipase in Adipose Tissue and Muscle

Hormone-sensitive lipase (HSL) is believed to play an important role in the mobilization of fatty acids from triglycerides (TG), diglycerides, and cholesteryl esters in various tissues. Because HSL-mediated lipolysis of TG in adipose tissue (AT) directly feeds non-esterified fatty acids (NEFA) into the vascular system, the enzyme is expected to affect many metabolic processes including the metabolism of plasma lipids and lipoproteins. In the present study we examined these metabolic changes in induced mutant mouse lines that lack HSL expression (HSL-ko mice). During fasting, when HSL is normally strongly induced in AT, HSL-ko animals exhibited markedly decreased plasma concentrations of NEFA (-40%) and TG (-63%), whereas total cholesterol and HDL cholesterol levels were increased (+34%). Except for the increased HDL cholesterol concentrations, these differences were not observed in fed animals, in which HSL activity is generally low. Decreased plasma TG levels in fasted HSL-ko mice were mainly caused by decreased hepatic very low density lipid lipoprotein (VLDL) synthesis as a result of decreased NEFA transport from the periphery to the liver. Reduced NEFA transport was also indicated by a depletion of hepatic TG stores (-90%) and strongly decreased ketone body concentrations in plasma (-80%). Decreased plasma NEFA and TG levels in fasted HSL-ko mice were associated with increased fractional catabolic rates of VLDL-TG and an induction of the tissue-specific lipoprotein lipase (LPL) activity in cardiac muscle, skeletal muscle, and white AT. In brown AT, LPL activity was decreased. Both increased VLDL fractional catabolic rates and increased LPL activity in muscle were unable to provide the heart with sufficient NEFA, which led to decreased tissue TG levels in cardiac muscle. Our results demonstrate that HSL deficiency markedly affects the metabolism of TG-rich lipoproteins by the coordinate down-regulation of VLDL synthesis and up-regulation of LPL in muscle and white adipose tissue. These changes result in an "anti-atherogenic" lipoprotein profile.

Regulation of messenger ribonucleic acid expression for gluconeogenic enzymes during glucagon infusions into lactating cows.

The effects of glucagon infusions on expression of mRNA for enzymes that regulate gluconeogenesis were studied in lactating cows. Normal cows and cows with fatty liver that were susceptible to ketosis were assigned to either glucagon-treated or control groups. Glucagon at 0 or 10 mg/d was infused for 14 d beginning at d 21 postpartum. In normal cows, glucagon infusions increased concentrations of both plasma glucagon and glucose, which caused plasma insulin to increase. Consequently, hepatic phosphoenolpyruvate carboxykinase mRNA decreased during wk 1 of glucagon infusions. Glucagon infusions into cows with fatty liver also increased plasma glucagon and glucose, but concentrations of plasma insulin and hepatic phosphoenolpyruvate carboxykinase mRNA did not change. More phosphoenolpyruvate carboxykinase mRNA was present in the livers of cows with fatty liver than in livers of normal cows. In a follow-up experiment with midlactation cows, 3.5-h infusions of glucagon at 14 mg/d increased plasma glucose and insulin and decreased plasma nonesterified fatty acids and hepatic glycogen. Hepatic phosphoenolpyruvate carboxykinase mRNA was decreased 41%, pyruvate carboxylase mRNA was increased 50%, but fructose-1,6-bisphosphatase mRNA did not change. We conclude that the expression of the hepatic phosphoenolpyruvate carboxykinase gene in normal cows is inhibited by insulin to balance elevated carbohydrate status during glucagon infusions; however, inhibited expression of hepatic phosphoenolpyruvate carboxykinase mRNA probably is not involved in the pathogenesis of lactation ketosis.

Effect of propylene glycol supplementation around parturition on milk yield, reproduction performance and some hormonal and metabolic characteristics in dairy cows

Thirty-nine multiparous Holstein cows were used to measure the effect of propylene glycol treatment around parturition on milk yield, reproductive efficiency and some hormone and metabolite concentrations. Cows were assigned randomly to control (n = 19) or propylene glycol treated (n = 20) groups. Propylene glycol (300 g) was administered directly mixed with the diet from day 10 prior to the expected calving date until parturition (day 0) and orally after dilution in 1 l water on days 3, 6, 9 and 12. Blood samples were collected on days -20, -5, 0, 3, 10, 25 and 50 while milk samples were taken weekly until 13 weeks post partum. Body condition scores, recorded on days -20, 15 and 50, were not affected by propylene glycol administration. Propylene glycol did not significantly affect milk yield or composition but linear somatic cell score measured from the first 13 weeks post partum was reduced by propylene glycol administration (P < 0.01). Moreover, propylene glycol reduced milk urea (-25 mg/l, P < 0.05), especially during the first 9 weeks post partum. Plasma insulin concentrations were similar in both groups during the experiment while insulin-like growth factor I (P < 0.05) and insulin-like growth factor-binding protein 3 (P < 0.001) levels were higher on days 10, 25 and 50 post partum in the propylene glycol group. Propylene glycol administration decreased plasma non-esterified fatty acid concentrations (P < 0.05 to P < 0.01) but increased total cholesterol levels (P < 0.01) after parturition while 3-hydroxybutyrate levels were unaffected by the treatment. Changes in the hormone and metabolic concentrations after propylene glycol administration in the last few days of gestation and the first week of lactation seem to indicate that energy balance in the treated group was probably more positive than in the control group. There was also evidence that propylene glycol administration prevented fatty liver syndrome and hastened the resumption of oestrous cycles (P < 0.001).