Ontogenesis of mRNA levels and binding sites of hepatic alpha-adrenoceptors in young cattle

Catecholamines affect hepatic glucose production through (alpha- and beta2-) adrenoceptors (AR). We studied mRNA abundance and binding of hepatic alpha-AR in pre-term (P0) calves and in full-term calves at day 0 (F0), day 5 (F5) and day 159 (F159) to test the hypothesis that gene expression and numbers of hepatic alpha-AR in calves are influenced by age and associated with beta2-AR and selected traits of glucose metabolism. mRNA levels of alpha1- and alpha2-AR were measured by real time RT-PCR. alpha1- and alpha2-AR numbers (maximal binding, Bmax) were determined by saturation binding of (3H)-prazosin and (3H)-RX821002, respectively. alpha1- and alpha2-AR subtypes were evaluated by competitive binding. alpha1A-AR mRNA levels were lower in P0 than in F0, F5 and F159 and alpha(2AD)-AR mRNA levels were lower in F159 than in P0, F0 and F5, while alpha2C-AR mRNA levels increased from P0 and F0 to F5 and F159. Bmax of alpha1-AR increased from P0 to F5, then decreased in F159. Bmax of alpha2-AR decreased from F0 to F159. Bmax of alpha1-AR was positively associated with mRNA levels of alpha1A-AR (r = 0.7), Bmax of beta2-AR (r = 0.5) and negatively with hepatic glycogen content (r = -0.6). Bmax of alpha2-AR was negatively associated with Bmax of beta2-AR (r = -0.4). In conclusion, mRNA levels and binding sites of alpha1- and alpha2-AR in calves exhibited developmental changes and were negatively associated with hepatic glycogen content.     

Ontogeny of mRNA abundance of nuclear receptors and nuclear receptor target genes in young cattle

After birth the development of appropriate detoxification mechanisms is important. Nuclear receptors (NR), such as constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor-alpha (PPARalpha), retinoid receptors (RAR, RXR), and NR target genes are involved in the detoxification of exogenous and endogenous substances. We quantified abundances of hepatic mRNA of NR and several NR target genes (cytochromes, CYP; cytochrome P450 reductase, CPR; UDP-glucuronosyl transferase, UDP) in calves at different ages. Gene expression was quantified by real-time RT-PCR. Abundance of mRNA of CAR and PXR increased from low levels at birth in pre-term calves (P0) and full-term calves (F0) to higher levels in 5-day-old calves (F5) and in 159-day-old veal calves (F159), whereas mRNA levels of PPARalpha did not exhibit significant ontogenetic changes. RARbeta mRNA levels were higher in F5 and F159 than in F0, whereas no age differences were observed for RARalpha levels. Levels of RXRalpha and RXRbeta mRNA were lower in F5 than in P0 and F0. Abundance of CYP2C8 and CYP3A4 increased from low levels in P0 and F0 to higher levels in F5 and to highest levels in F159. Abundance of CPR was transiently decreased in F0 and F5 calves. Levels of UGT1A1 mRNA increased from low levels in P0 and F0 to maximal level in F5 and F159. In conclusion, mRNA levels of NR and NR target genes exhibited ontogenetic changes that are likely of importance for handling of xeno- and endobiotics with increasing age.     

Dexamethasone and colostrum feeding affect hepatic gluconeogenic enzymes differently in neonatal calves

Plasma glucose concentrations in neonates are influenced by colostrum feeding and by glucocorticoids. We have tested whether a high-glucocorticoid status after birth, as well as colostrum feeding, influences glucose metabolism in association with changes of hepatic expression and activities of gluconeogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK; EC 4.1.1.32) and pyruvate carboxylase (PC; EC 6.4.1.1) in neonatal calves. Calves (n = 14 per group) were fed either colostrum or a milk-based formula with nutrient and energy contents similar to colostrum. Half the calves in each feeding group were treated with dexamethasone (DEXA; 30 microg/[kg BW x d]). Pre- and postprandial blood samples were taken on d 1, 2, 4, and 5 and liver samples were collected on d 5 of life. Dexamethasone treatment increased (P < or = 0.05) plasma concentrations of glucose, insulin, and glucagon more in colostrum-fed than in formula-fed calves but increased (P < or = 0.05) urea concentrations and decreased (P < or = 0.05) concentrations of NEFA, ACTH, and cortisol independent of colostrum vs. formula feeding. Colostrum feeding increased (P < 0.05) plasma glucose, but decreased (P < 0.05) plasma urea concentrations. Glucagon-to-insulin ratios in DEXA-treated and colostrum-fed calves were decreased (P < 0.05). Dexamethasone treatment decreased hepatic mRNA levels and activities of PC (P < 0.001 and P < 0.10) and activities of PEPCK (P < 0.001) but increased (P < 0.001) the glycogen content. Colostrum feeding increased (P < 0.05) mitochondrial PEPCK mRNA levels and PEPCK activities in calves not treated with DEXA but decreased (P < 0.1) amounts of PC mRNA. In conclusion, increased plasma glucose concentrations after DEXA treatment were not associated with a stimulation of hepatic gluconeogenic enzyme activities; however, colostrum feeding probably raised plasma glucose concentrations because of increased hepatic gluconeogenic activities.     

Response to ractopamine-hydrogen chloride is similar in yearling steers across days on feed

Yearling steers (n = 2,552; 314 kg of initial BW) were used to evaluate the effects of ractopamine-HCl (RAC) and days on feed on performance, carcass characteristics, and skeletal muscle gene expression in finishing steers. Treatment groups included serial slaughter dates of 150, 171, or 192 d on feed. Within each slaughter date, steers either received RAC (200 mg/steer) daily for the final 28 d or were not fed RAC. All steers were initially implanted with Revalor-IS and were reimplanted with Revalor-S after 75 d on feed. At slaughter, muscle samples from the semimembranosus were collected for mRNA analysis of the beta-adrenergic receptors (beta-AR). Ractopamine administration increased (P < 0.05) ADG, G:F, and HCW and increased (P = 0.08) LM area. Ractopamine did not affect the dressing percentage, USDA yield grade, or quality grade (P > 0.3). There was no change in overall feed intake across the entire feeding period; however, feed intake was increased during the 28-d period during which the steers were fed RAC (P < or = 0.05). Greater days on feed decreased (P < 0.05) ADG, G:F, DMI, and the number of yield grade 1 and 2 carcasses. Also, greater days on feed increased (P < 0.05) HCW, dressing percentage, and the number of prime and choice carcasses, as well as the number of yield grade 4 and 5 carcasses. Increasing days on feed decreased (P < 0.05) the abundance of beta(1)-AR and beta(3)-AR mRNA and increased (P < 0.05) the abundance of beta(2)-AR mRNA in skeletal muscle samples obtained at slaughter. Ractopamine had no effect (P > 0.10) on the abundance of beta(1)-AR or beta(3)-AR mRNA, but tended (P = 0.09) to increase beta(2)-AR mRNA. Additional time-course studies with primary muscle cell cultures revealed that advancing time in culture increased (P < 0.001) beta(2)-AR mRNA but had no effect (P > 0.10) on beta(1)-AR or beta(3)-AR mRNA. We conclude that days on feed and RAC are affecting beta-AR mRNA levels, which could, in turn, impact the biological response to RAC feeding in yearling steers.     

Differential response of cull cow muscles to the hypertrophic actions of ractopamine-hydrogen chloride

Ractopamine-HCl (RAC) is a beta-adrenergic agonist with variable effects on cattle performance and carcass variables. Cull cows fed RAC (200 mg . head(-1) . d(-1)) demonstrate an increased size of type I and II muscle fibers that does not translate into a larger ribeye area. The objective of this study was to examine the dose-dependent effects of RAC on cull cow muscle morphometrics. Eighty-eight cull beef cows representing 2 breed types (n = 44 each) were fed 0, 100, 200, and 300 mg . head(-1) . d(-1) of RAC for the last 28 d of a 54-d feeding period. On d 54, cows were slaughtered, and samples of the LM and semimembranosus muscle (SM) from 16 randomly selected carcasses (n = 4 per treatment) were taken for measurement of beta (2)-adrenergic receptors and type I, IIA, and IIX myosin heavy chain (MyHC) gene expression. Twenty-four hours postmortem, LM, SM, infraspinatus (INF), and vastus lateralis samples from 40 randomly selected carcasses (n = 10 per treatment) were obtained and frozen for immunohistochemical analysis. Muscle fiber cross-sectional area and diameter, MyHC isoform expression, and fiber-associated nuclei numbers were measured. Ractopamine dosage exhibited differential effects on muscle morphometrics and MyHC gene expression. Muscle fiber cross-sectional area and diameter were increased (P < 0.05) by RAC in INF type I and IIA fibers and SM type IIA fibers. Ractopamine increased (P < 0.05) MyHC type IIX mRNA and tended to increase (P < 0.10) beta(2)-adrenergic receptors in the SM; a change in mRNA abundance was not detected for either gene in the LM. Treatment with RAC decreased (P < 0.05) fiber-associated nuclei numbers in the INF, vastus lateralis, and LM but did not affect (P > 0.05) MyHC or beta-adrenergic receptor expression. These results indicate that cull cow feeding programs may consider supplementing RAC as a means of adding value to cuts within the chuck, such as the INF.     

Effect of feedlot management system on response to ractopamine-HCl in yearling steers

Two experiments evaluated the effects of conventional and natural feedlot management systems (MS) on ractopamine-HCl (RAC) response in yearling steers. Feedlot performance, carcass characteristics, skeletal muscle gene expression, and circulating IGF-I concentrations were measured. The conventional system included a combined trenbolone acetate and estradiol implant, Revalor-S (IMP), as well as monensin-tylosin feed additives (IA). Treatments were arranged in a 2 x 2 factorial and included: 1) natural (NAT): no IMP-no IA, no RAC; 2) natural plus (NAT+): no IMP-no IA, RAC; 3) conventional (CON): IMP-IA, no RAC; and 4) conventional plus (CON+): IMP-IA, RAC. In Exp. 1, one hundred twenty crossbred steers (initial BW = 400 +/- 26 kg) were allotted randomly to treatment in a randomized complete block design (BW was blocking criteria); pen was the experimental unit. In Exp. 2, twenty-four individually fed crossbred steers (initial BW = 452 +/- 25 kg) were used in a randomized complete block design (BW was blocking criteria) and assigned to the same treatments as Exp. 1, with 6 steers/treatment. In Exp. 2, serum was harvested on d 0 and 31 and within the 28-d RAC feeding period, at d 0, 14, and 28. Longissimus biopsy samples were taken on d 0, 14, and 28 of the RAC feeding period for mRNA analysis of beta-adrenergic receptors and steady-state IGF-I mRNA. In Exp. 1, ADG, G:F, final BW, and HCW were greatest for CON+ (P < 0.01). During the final 37 d, RAC increased ADG (P = 0.05) and increased overall G:F (P = 0.02). Marbling score was reduced (P = 0.02), and yield grade was improved with RAC (P = 0.02), but RAC did not affect dressing percentage (P = 0.96) or HCW (P = 0.31). In Exp. 2, MS x RAC interactions were detected in ADG and G:F the last 28 d, overall ADG and overall G:F, final BW, and HCW (P < 0.01). Dressing percentage, yield grade, and marbling score were not altered by MS or RAC (P > 0.10). Circulating IGF-I concentration was increased on d 31 by the conventional MS, and concentration was greater throughout the study than NAT steers (P < 0.01). Circulating IGF-I concentrations were not changed by RAC (P = 0.49). Abundance of beta(1)-AR mRNA tended to increase (P = 0.09) with RAC, but RAC did not affect beta(2)-AR, beta(3)-AR, or IGF-I mRNA (P > 0.40). Management system did not affect beta(1)-AR, beta(2)-AR, beta(3)-AR, or IGF-I mRNA (P > 0.18), yet a trend (P = 0.06) for MS x RAC for beta(2)-AR mRNA was detected. These results indicate that response to RAC is affected by feedlot management practices.     

Muscarinic receptor subtypes, β-adrenoceptors and cAMP in the tracheal smooth muscle of conventional and double-muscled calves

The total muscarinic (M₁ + M₂ + M₃) and -adrenergic receptors in the tracheal smooth muscle of conventional and double-muscled calves were identified and characterized with the non-specific antagonists [³H]quinuclidinyl benzilate ([³H]QNB) and [³H]dihydroalprenolol ([³H]DHA) respectively.Although the quantity of -adrenoceptors in double-muscled calves was 25% lower (p<0.05) than in conventional calves (B _max=327±89 fmol/mg protein), adenylate cyclase assays indicated that the basal adenylate cyclase activity and the (–)-isopropylnoradrenaline (ISO)- and sodium fluoride (NaF)-stimulated values were not significantly different between these calves. However, the density of muscarinic receptors in double-muscled calves was 40% higher (p<0.01) than in conventional calves (B _max=2955±625 fmol/mg protein). Subtypes of muscarinic receptors were studied with [³H]telenzepine (M₁-receptors), [³H]AF-DX 384 (M₂-receptors) and [³H]4DAMP (M₁ and M₃-receptors). It was found that in both double-muscled and conventional calves about 40% of the receptors were of the M₃-subtype, the remaining 60% being M₂-receptors.From these results, it is suggested that inflammation of the respiratory tract in double-muscled calves may be complicated by an imbalance between the cholinergic bronchoconstrictor and the -adrenergic bronchodilator components of the autonomic nervous system.     

Response to ractopamine-HCl in heifers is altered by implant strategy across days on feed

Two experiments were conducted to investigate the effects of ractopamine-HCl (RAC) and implant strategy or days on feed (DOF) on feedlot performance and expression of beta-adrenergic receptors (AR). In Exp. 1, 1,147 feedlot heifers weighing 282 +/- 3 kg were used with implant treatments of Revalor-200 (R200) at arrival, or Revalor-IH at arrival with reimplantation with Finaplix-H on d 58 (RF). Ractopamine (0 vs. 200 mg/d) was fed the last 28 d in both experiments. Treatments were randomly assigned to 16 pens. At slaughter, semimembranosus muscle tissue was excised for RNA isolation. Ractopamine administration increased (P < 0.05) ADG, G:F, HCW, and LM; decreased (P < 0.05) 12th rib fat depth; and improved (P < 0.05) yield grade. There was no effect (P > 0.10) on the expression of beta1-AR mRNA; however, there was a tendency (P = 0.10) for RAC feeding to increase beta2-AR mRNA levels. For beta3-AR mRNA, there was an implant by RAC interaction (P = 0.05), with RAC numerically increasing beta3-AR mRNA in heifers implanted with RF, but a decrease (P < 0.05) in expression in heifers implanted with R200. Ractopamine also decreased (P < 0.05) IGF-I mRNA in heifers implanted with RF. In Exp. 2, 2,077 heifers were used to investigate the effects of RAC and DOF. Days on feed were 129, 150, and 170, and RAC was administered the last 28 d. Ractopamine improved (P < 0.05) G:F, but had no other effects (P > 0.05) on performance. Average daily gain decreased (P < 0.05) as DOF increased. Hot carcass weight, LM area, 12th rib fat, G:F, calculated yield grade, and marbling score increased (P < 0.05) and the percentage of KPH fat decreased (P < 0.05) as DOF increased. These data aid in our understanding of the effects of steroidal implants, DOF, and RAC administration in feedlot heifers.     

Allometric analysis of thiamphenicol disposition among seven mammalian species

The pharmacokinetics of thiamphenicol (TAP), a broad-spectrum antibiotic, was determined in male mice, rats, rabbits, dogs, pigs, sheep and calves. The relationship between the main pharmacokinetic parameters of TAP and body weight (W) was studied across these seven mammalian species, using double-logarithmic plots. The experimental values of volume of distribution (Vss), clearance (Cl) and elimination half-life (t(1/2)beta) were plotted, and extrapolated values were determined from corresponding allometric equations. These parameters were fitted to the following equations: Vss=0.98W0.92, Cl=15.80W0.76 and t(1/2)beta=0.94W0.20, and present good correlation (Vss: r2=0.997, P < 0.001; Cl: r2=0.976, P < 0.001, t(1/2)beta: r2=0.852, P < 0.005), that is expected of a drug eliminated primarily by renal glomerular filtration, with insignificant hepatic metabolism. For the t(1/2)beta, the extrapolated and observed values were similar. The extrapolated values of Cl were close to the experimental values, except for the mouse and pig mean percent error [(M.E.) equal to 62 and 119%, respectively], while the extrapolated and observed values for the Vss were very similar. The comparison between experimental and extrapolated values suggests that it could be possible to extrapolate, with good prediction, the kinetic parameters of this drug for mammalian species, using allometric scaling, except for the species that eliminate the drug by a combination of renal excretion and hepatic metabolism.     

Beta-adrenergic receptor activity in ponies with recurrent obstructive pulmonary disease.

Pulmonary function measurements were made in control ponies and in ponies with recurrent obstructive pulmonary disease (principals) during clinical remission and during an attack of acute airway obstruction. The ponies were given beta-adrenergic antagonists and agonists to determine the role of beta receptors in recurrent obstructive pulmonary disease, and to determine the subtypes of beta receptors mediating bronchodilation in ponies. Aerosol administration of the beta antagonists, propranolol (beta 1 and beta 2), atenolol (beta 1), and butoxamine (beta 2) decreased dynamic compliance (Cdyn) and increased pulmonary resistance (RL) in the principal ponies during airway obstruction, but were without effect when the ponies were in clinical remission. Intravenous administration of atropine reversed the effect of atenolol on Cdyn and RL, but was without effect on the decrease in Cdyn and increase in RL observed after butoxamine administration. The beta antagonists did not affect airway function in the control ponies. The effect of beta blockade on Cdyn and RL suggests beta-adrenergic activation in the central and peripheral airways of principal ponies, mediated through both beta 2- and beta 1-adrenergic receptors. The aerosol beta agonists, isoproterenol (beta 1 and beta 2), and clenbuterol (beta 2) attenuated histamine-induced airway obstruction to a similar extent in control ponies that were given histamine IV. In addition, the beta 1 antagonist, atenolol, did not attenuate the bronchodilation observed with isoproterenol. We concluded that, although beta 1- and beta 2-adrenergic receptors exist in pony airways and are activated during acute airway obstruction, bronchodilation in response to beta agonists in ponies seems to be mediated primarily by beta 2-adrenergic receptors.     

Effect of nutrient intake on the development of the somatotropic axis and its responsiveness to GH in Holstein bull calves

We investigated the effect of increasing nutrient intake on the responsiveness of the GH/IGF-I system in calves fed a high-protein milk replacer. Fifty-four Holstein bull calves were fed one of three levels (low, medium, and high; n = 18 per treatment) of a 30% crude protein, 20% fat milk replacer to achieve target rates of gain of 0.50, 0.95, or 1.40 kg/d, respectively, for low, medium, and high. Six calves per treatment were slaughtered at approximately 65, 85, and 105 kg BW. Additionally, six calves were slaughtered at 1 d of age to provide baseline data. Plasma aliquots from blood samples collected weekly were analyzed for IGF-I, insulin, glucose, NEFA, and plasma urea nitrogen (PUN). Plasma IGF-I and insulin, measured weekly, increased (P < 0.001) with greater nutrient intake from wk 2 of life to slaughter. Plasma glucose and NEFA also increased (P < 0.05) with nutrient intake. In addition, each calf underwent a GH challenge beginning 4 d before the scheduled slaughter. Plasma from blood collected before the first GH injection and 14 and 24 h after the third injection was analyzed for IGF-I and PUN. Response to challenge, calculated as the absolute difference between the prechallenge and 14-h postchallenge plasma IGF-I concentrations, was significant in calves on all three treatments. Plasma urea nitrogen was not different among treatments as measured weekly but decreased (P < 0.001) following GH challenge in all calves. Results of ribonuclease protection assays showed increased expression of hepatic mRNA for GH receptor 1A and IGF-I with increased intake. The amounts of GH receptor and IGF-I mRNA in muscle and adipose, however, were not affected by intake. In summary, plasma IGF-I was elevated in calves with increased nutrient intake, and the elevations in plasma IGF-I following short-term administration of GH were significant in all calves by 65 kg BW. Data demonstrate that in well-managed milk-fed calves the somatotropic (GH/IGF-I) axis is functionally coordinated and sensitive to nutrient intake and GH.     

Abundance of message for insulin-like growth factors-I and -II and for receptors for growth hormone,insulin-like growth factors-I and -II,and insulin in the intestine and liver of pre- and full-term calves

The somatotropic axis and insulin are involved in pre- and postnatal development. In pre- and full-term calves (GrP0 and GrN0; born after 277 and 290 d of pregnancy, respectively) and in preterm calves on d 8 of life after being fed for 7 d (GrP8), we studied whether there are differences in the abundance of messenger RNA (mRNA) of IGF-I and IGF-II and of receptors for GH, IGF-I, IGF-II, and insulin among different intestinal sites (duodenum, jejunum, ileum, and colon) and whether there are ontogenetic differences during the perinatal period in intestine and liver. Intestinal site differences (P < 0.05) existed in mRNA levels of IGF-I and IGF-II and receptors for GH, IGF-I, IGF-II, and insulin. Abundance of mRNA of IGF-I and -II and of receptors for IGF-I and GH was highest (P < 0.05) in the colon, abundance of the receptor for IGF-II was comparably high in the colon and ileum, and that of the receptor for insulin was similarly high in colon, ileum, and jejunum. Among GrP0, GrN0, and GrP8 groups, there were differences (P < 0.05) in mRNA levels of IGF-I and IGF-II and of receptors for GH, IGF-I, IGF-II and insulin. Abundance of mRNA of IGF-I and IGF-II and of receptors for GH, IGF-I, IGF-II and insulin was highest (P < 0.05) in GrP0 calves immediately after birth and was primarily seen in the ileum. In liver, the mRNA levels differed (P < 0.05) among groups for IGF-II and receptors for IGF-I, IGF-II, and insulin, and were highest (P < 0.05) for IGF-II in GrP0, for receptors of IGF-I in GrN0, and were higher (P < 0.05) in GrP0 than GrP8 for receptors of IGF-II. In conclusion, mRNA levels of IGF-I and IGF-II and of receptors for GH, IGF-I, IGF-II, and insulin were different at different intestinal sites and in intestine and liver and changed during the perinatal period.     

Metabolic adaptations associated with irreversible glucose loss are different to those observed during under-nutrition

In this study the hypothesis that irreversible glucose loss results in an 'uncoupling' of the somatotrophic axis (increasing plasma GH levels and decreasing plasma IGF-I) was tested. During periods of negative energy balance the somatotrophic axis respond by increasing plasma GH and decreasing plasma IGF-I levels. In turn, elevated GH repartitions nutrient by increasing lipolysis and protein synthesis, and decreases protein degradation. Irreversible glucose loss was induced using sub-cutaneous injections of phloridizin. Seven non-lactating cows were treated with 8g/day phloridizin (PHZ) and seven control animals (CTRL, 0g/day), while being restricted to a diet of 80% maintenance. PHZ treatment increased urinary glucose excretion (P<0.001), resulting in hypoglycemia (P<0.001). As a response to this glucose loss, the PHZ treated animals had elevated plasma NEFA (P<0.005) and BHBA (P<0.001) levels. Average plasma insulin concentrations were not altered with PHZ treatment (P=0.059). Plasma GH was not different between the two groups (P>0.1), whereas plasma IGF-I levels decreased significantly (P<0.001) with PHZ treatment. The decline in plasma IGF-I concentrations was mirrored by a decrease in the abundance of hepatic IGF-I mRNA (P=0.005), in addition the abundance of hepatic mRNA for both growth hormone receptors (GHR(tot) and GHR(1A)) was also decreased (P<0.05). Therefore, the irreversible glucose loss resulted in a partial 'uncoupling' of the somatotrophic axis, as no increase in plasma GH levels occurred although plasma IGF-I levels, hepatic IGF-I mRNA declined, and the abundance of liver GH receptor mRNA declined.     

The influence of clenbuterol on prostaglandin F2 alpha-induced dyspnoea in calves

Pulmonary function tests were performed in six healthy calves. Prostaglandin F2 alpha causes severe narrowing of both upper and lower airways (total lung resistance increased, dynamic compliance decreased). Clenbuterol administered intravenously fifteen minutes prior to prostaglandin F2 alpha aerosol, and in increasing doses (0, 0.4, 0.8, 1.2 micrograms/kg), on days 1, 2, 4 and 6 of the experiment, effectively but not entirely suppressed these responses. These data indicate that beta-adrenergic receptors are present in the bovine airways and that the use of clenbuterol (0.8 micrograms/kg) may be effective in treating clinical respiratory disease such as bronchopneumonia in calves.     

Duration of feeding linseed diet influences expression of inflammation-related genes and growth performance of growing-finishing barrows

The aim of the study was to investigate the effects of dietary linseed (rich in n-3 PUFA) on expression of inflammation-related genes and on growth performance of growing-finishing barrows. Two isoenergetic and isonitrogenous diets were formulated, one as the basal diet and the other containing 10% linseed. Twenty-four Landrace x Yorkshire barrows weighing 35 +/- 3.7 kg were randomly assigned to 1 of 4 treatment groups, with 6 pigs per group. During the entire experimental period of 90 d, these 4 groups of pigs were first fed the basal diet and then fed the linseed diet for 0, 30, 60, and 90 d before slaughter, respectively. Pig growth; messenger RNA (mRNA) expression of peroxisome proliferator-activated receptor-gamma (PPARgamma), IL-1beta0, IL-6, and tumor necrosis factor-alpha (TNF-alpha); and plasma concentrations of the 3 proinflammatory cytokines were measured and analyzed. Average daily feed intake did not differ among treatment groups (P > 0.05), but ADG (P < 0.05) and G:F (P < 0.01) responded quadratically to the duration of linseed diet feeding, and pigs in the 60-d treatment group had the greatest ADG and G:F. The mRNA expression of PPARgamma in loin muscle and spleen increased linearly (P < 0.01) with the duration of linseed diet feeding, whereas its expression in adipose tissue was not affected (P = 0.095). Tumor necrosis factor-alpha and IL-6 mRNA expression in muscle, adipose, and spleen, as well as serum concentration of TNF-alpha, decreased linearly (P < 0.01) with the duration of linseed diet feeding. Peroxisome proliferator-activated receptor-gamma mRNA abundance was negatively correlated with IL-1beta, IL-6, and TNF-alpha mRNA abundance both in muscle (R(2) = 0.63, P < 0.001) and in spleen (R(2) = 0.69, P < 0.001), and PPARgamma mRNA expression in spleen (R(2) = 0.59, P < 0.01) and muscle (R(2) = 0.52, P < 0.05) was negatively correlated with serum TNF-alpha concentration. There were also significant quadratic relations between ADG and expression of PPARgamma (P < 0.05) and splenic TNF-alpha (P < 0.05). These data suggest that intake of n-3 PUFA from the linseed diet led to significant decreases in the expression of proinflammatory cytokine genes, which may stimulate growth in growing-finishing barrows, at least in part, through a PPARgamma-dependent mechanism.