The neonatal pig ranks among the most prominent research models for the study of pediatric nutrit... more The neonatal pig ranks among the most prominent research models for the study of pediatric nutrition and metabolism. Its precocial development at birth affords ready adaptation to artificial rearing systems, and research using this model spans a wide array of nutrients. Sophisticated in vitro and in vivo methodologies supporting both invasive, reduction-science research as well as whole-animal preclinical investigations have been developed. Potential applications may dually benefit both agricultural and medical sciences (e.g., "agrimedical research"). The broad scope of this review is to outline the fundamental elements of the piglet model and to highlight key aspects of relevance to various macronutrients, including lipids, carbohydrates, proteins/amino acids, and calcium/phosphorus. The review examines similarities between piglets and infants and also piglet idiosyncrasies, concluding that, overall, the piglet represents an adaptable and robust model for pediatric nutrit...
The objective of this study was to evaluate the effects of clofibrate on gene expression of hepat... more The objective of this study was to evaluate the effects of clofibrate on gene expression of hepatic fatty‐acid‐oxidation and ketogenesis enzymes induced in pigs during neonatal development. Evaluations were conducted in 0, 1, 4 and 7 d‐old pigs fed milk replacer and orally gavaged with either vehicle (2 % Tween 80) or clofibrate (75 mg /kg body weight) +/‐ etomoxir (5 mg/ kg body weight). Transcript abundances were measured using qRT‐PCR and were greater for carnitine palmitoyltransfersae I (CPT I; 2.8 fold), carnitine palmitoyltransfersae II (CPT II; 3.1 fold), and mitochondrial 3‐methly‐3‐hydroxyglutaryl‐CoA synthase (mHMG‐CoA‐S; 3.9 fold) in pigs fed clofibrate verses vehicle. Addition of etomoxir had no effects on the transcript abundances induced by clofibrate. Transcript abundance of targeted genes also increased as piglets aged, but the mRNA levels remained relatively constant for CPT I and mHMG‐CoA‐S in pigs after 4 d and for CPT II after 1 d. There was no interaction betwee...
This study evaluated the effects of supplementation of ARA on delta‐6‐desaturase (D6D) and delta‐... more This study evaluated the effects of supplementation of ARA on delta‐6‐desaturase (D6D) and delta‐5‐desaturase (D5D) mRNA abundance and synthesis of ARA in the intestine and liver. Day old pigs (n=96) were fed a milk based formula for 4, 8, and 16 d. Diets contained either no polyunsaturated fatty acids (0% ARA, negative control), 0.5% ARA, 2.5% ARA, 5% ARA or 5% eicosapentaenoic acid (EPA) of total fatty acids. A sow fed reference group (SRC n=18) also was included. The mRNA relative abundance increased differentially (diet x age interaction, P < 0.05) from d4 to d16 in pigs fed 0.5% (D6D‐55%, D5D‐66%) versus 5% (D6D‐60%, D5D‐64%) ARA diets in the intestine. Transcript abundance of D6D and D5D were not affected by diet in the liver (P>0.05), however, there was a precipitous decrease between birth and d4 (~5‐fold, P<0.05). To measure flux through the desaturase‐elongase pathway we incubated liver and intestinal mucosa with 13C‐linoleate(C18:2, n‐6) and traced its metabolism ...
A neonatal piglet model was used to study hepatic fatty acid metabolism during the early postnata... more A neonatal piglet model was used to study hepatic fatty acid metabolism during the early postnatal period. Hepatocytes were isolated from pigs at birth or after 24 h, in fed or unfed states (n = 4 pigs/group). Cells were incubated with 1 mmol/L [1-(14)C]-octanoate (C8) or -palmitate (C16) in the presence or absence of 1 mmol/L L-carnitine, carnitine plus tetradecylglycidic acid (TDGA; 10 mumol/L) or carnitine plus glucagon (0.5 microgram/L). Accumulation of radiolabel [nmol/(h. 10(6) cells)] in CO2 and acid-soluble products (ASP) was higher (3.5- and 4.5-fold, respectively) from C8 than from C16 (P < 0.0001). Glucagon, carnitine and TDGA had no effect on the oxidation of C8 (P > 0.1). Carnitine addition tended to increase C16 flux to ASP [from 5.3 to 7.6 nmol/(h. 10(6) cells); P < 0.1], whereas carnitine plus TDGA decreased flux (from 7.6 to 2.1; P < 0.001). Esterified products accounted for 70% of metabolized label in control C16 incubations; this was reduced to 62% by ...
We hypothesized that methylated fatty acids (e.g. 2-methylpentanoic acid (2MeP), phytanic or pris... more We hypothesized that methylated fatty acids (e.g. 2-methylpentanoic acid (2MeP), phytanic or pristanic acids) would provide anaplerotic carbon to the tricarboxylic acid (TCA) cycle and thereby enha...
American Journal of Physiology-Endocrinology and Metabolism, 1998
The current studies were performed to better understand the physiological relevance of acetate in... more The current studies were performed to better understand the physiological relevance of acetate in the poorly ketogenic piglet and to determine if endogenous acetogenesis rises with increased mitochondrial fatty acid β-oxidation, analogous to ketogenesis. Plasma acetate concentration values in newborn, fasted, or suckled piglets (230–343 μM) were at least 10-fold higher than the ketone bodies, a pattern opposite to that in 24- to 48-h suckled rats (77–175 μM). Employing continuous infusion techniques with sodium [3H]acetate tracer in fasting ∼40-h-old piglets, acetate rate of appearance (Ra) was found to be 34 ± 4 μmol ⋅ min−1⋅ kg body wt−1. This basal Rawas double that observed in animals coinfused with sodium [1-14C]hexanoate ( P < 0.001), despite active oxidation of the latter as determined by14CO2production. Active acetogenesis in vivo and relatively abundant acetate in piglet blood are consistent with the hypothesis that acetate plays an important physiological role in piglet...
Two studies were designed to determine the effects of supplementing diets with lipid sources of E... more Two studies were designed to determine the effects of supplementing diets with lipid sources of EFA (linoleic and α-linolenic acid) on sow milk composition to estimate the balance of EFA for sows nursing large litters. In Exp. 1, 30 sows, equally balanced by parity (1 and 3 to 5) and nursing 12 pigs, were fed diets supplemented with 6% animal-vegetable blend (A-V), 6% choice white grease (CWG), or a control diet without added lipid. Diets were corn-soybean meal based with 8% corn distiller dried grains with solubles and 6% wheat middlings and contained 3.25 g standardized ileal digestible Lys/Mcal ME. Sows fed lipid-supplemented diets secreted greater amounts of fat (P = 0.082; 499 and 559 g/d for control and lipid-added diets, respectively) than sows fed the control diet. The balance of EFA was computed as apparent ileal digestible intake of EFA minus the outflow of EFA in milk. For sows fed the control diet, the amount of linoleic acid secreted in milk was greater than the amount ...
An experiment was conducted to explore the nature of the radiolabel distribution in acid-soluble ... more An experiment was conducted to explore the nature of the radiolabel distribution in acid-soluble products (ASPs) resulting from the oxidation of [1-14C]C7:0 or C8:0 by isolated piglet hepatocytes. The differences between odd and even chain-length and the impacts of valproate and malonate upon the rate of β-oxidation and ASP characteristics were tested. A minor amount of fatty acid carboxyl carbon (⩽ 10% of organic acids identified by radio-HPLC) accumulated in ketone bodies regardless of chain-length or inhibitor used. In all cases, acetate represented the major reservoir of carboxyl carbon, accounting for 60–70% of radiolabel in identified organic acids. Cells given [1-14C]C7:0 accumulated 85% more carboxyl carbon in Krebs cycle intermediates when compared with C8:0, while accumulation in acetate was unaffected. The results are consistent with the hypothesis that anaplerosis from odd-carbon fatty acids affects the oxidative fate of fatty acid carbon. The piglet appears unique in th...
Utilization of energy-dense lipid fuels is critical to the rapid development and growth of neonat... more Utilization of energy-dense lipid fuels is critical to the rapid development and growth of neonates. To increase efficiency of milk fat utilization by newborn pigs, the effect of clofibrate on in vivo and in vitro long-chain fatty acid (LCFA) oxidation was evaluated. Newborn male pigs were administered 5 mL of vehicle (2% Tween 80) with or without clofibrate (75 mg/kg body weight) once daily via i.g. gavage for 4 d. Total LCFA oxidative capacity was measured in respiration chambers after gastric infusion (n = 5 per treatment) with isoenergetic amounts of [1-(14)C]triglycerides (TGs), either oleic acid (18:1n-9) TG [3.02 mmol/kg body weight (BW)(0.75)] or erucic acid (22:1n-9) TG (2.46 mmol/kg BW(0.75)). Total expired (14)CO2 was collected and quantified at 20-min intervals over 24 h. Hepatic in vitro LCFA oxidation was determined simultaneously using [1-(14)C]oleic acid and erucic acid substrates. The in vivo 24-h accumulative [1-(14)C]TG oxidation (percentage of energy intake/kg BW...
To investigate the effect of protein-energy malnutrition on intestinal barrier function during ro... more To investigate the effect of protein-energy malnutrition on intestinal barrier function during rotavirus enteritis in a piglet model. Newborn piglets were allotted at day 4 of age to the following treatments: (1) full-strength formula (FSF)/noninfected; (2) FSF/rotavirus infected; (3) half-strength formula (HSF)/noninfected; or (4) HSF/rotavirus infected. After one day of adjustment to the feeding rates, pigs were infected with rotavirus and acute effects on growth and diarrhea were monitored for 3 d and jejunal samples were collected for Ussing-chamber analyses. Piglets that were malnourished or infected had lower body weights on days 2 and 3 post-infection (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). Three days post-infection, marked diarrhea and weight loss were accompanied by sharp reductions in villus height (59%) and lactase activity (91%) and increased crypt depth (21%) in infected compared with non-infected pigs (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). Malnutrition also increased crypt depth (21%) compared to full-fed piglets. Villus:crypt ratio was reduced (67%) with viral infection. There was a trend for reduction in transepithelial electrical resistance with rotavirus infection and malnutrition (P = 0.1). (3)H-mannitol flux was significantly increased (50%; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) in rotavirus-infected piglets compared to non-infected piglets, but there was no effect of nutritional status. Furthermore, rotavirus infection reduced localization of the tight junction protein, occludin, in the cell membrane and increased localization in the cytosol. Overall, malnutrition had no additive effects to rotavirus infection on intestinal barrier function at day 3 post-infection in a neonatal piglet model.
Tryptophan (Trp), the rate-limiting substrate of serotonin [5-hydroxytryptoamine (5-HT)] synthesi... more Tryptophan (Trp), the rate-limiting substrate of serotonin [5-hydroxytryptoamine (5-HT)] synthesis in the brain, competes with large neutral amino acids (LNAA) to cross the blood-brain barrier. This study was designed to evaluate the effect of L-Trp supplementation on nursery pigs experiencing social-mixing stress and fed diets varying in LNAA concentrations. Forty-eight individually housed barrows at 6 wk of age were randomly allotted to 4 dietary treatments based on a 2 × 2 factorial arrangement, with L-Trp supplementation (0 or 0.6%) and LNAA concentrations (4.5 or 3.8%) as the 2 main factors. Pigs were fed the diets for 7 d. On d 4, pigs within a treatment were paired in a new pen to create social-mixing stress and behavior was recorded for 24 h. Body weight was measured on d 0, 4, 5, and 7. Saliva and blood were collected on d 4 and 7. On d 7, pigs were killed to obtain hypothalami. During the entire period excluding the mixing day (d 5), L-Trp supplementation improved (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) feed efficiency of pigs and lowering the LNAA further enhanced (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) the effects of L-Trp. Supplementation of 0.6% L-Trp increased (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) hypothalamic 5-HT and 5-hydroxyindoleacetic acid. The salivary cortisol concentration was reduced (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) by lowering the LNAA. Collectively, lowering the LNAA further enhanced the improvement of feed efficiency by L-Trp supplementation of nursery pigs under social-mixing stress in association with reduced stress hormones, indicating that reducing LNAA in the diet can facilitate the effect of L-Trp on the stress response of pigs.
The neonatal pig ranks among the most prominent research models for the study of pediatric nutrit... more The neonatal pig ranks among the most prominent research models for the study of pediatric nutrition and metabolism. Its precocial development at birth affords ready adaptation to artificial rearing systems, and research using this model spans a wide array of nutrients. Sophisticated in vitro and in vivo methodologies supporting both invasive, reduction-science research as well as whole-animal preclinical investigations have been developed. Potential applications may dually benefit both agricultural and medical sciences (e.g., "agrimedical research"). The broad scope of this review is to outline the fundamental elements of the piglet model and to highlight key aspects of relevance to various macronutrients, including lipids, carbohydrates, proteins/amino acids, and calcium/phosphorus. The review examines similarities between piglets and infants and also piglet idiosyncrasies, concluding that, overall, the piglet represents an adaptable and robust model for pediatric nutrit...
The objective of this study was to evaluate the effects of clofibrate on gene expression of hepat... more The objective of this study was to evaluate the effects of clofibrate on gene expression of hepatic fatty‐acid‐oxidation and ketogenesis enzymes induced in pigs during neonatal development. Evaluations were conducted in 0, 1, 4 and 7 d‐old pigs fed milk replacer and orally gavaged with either vehicle (2 % Tween 80) or clofibrate (75 mg /kg body weight) +/‐ etomoxir (5 mg/ kg body weight). Transcript abundances were measured using qRT‐PCR and were greater for carnitine palmitoyltransfersae I (CPT I; 2.8 fold), carnitine palmitoyltransfersae II (CPT II; 3.1 fold), and mitochondrial 3‐methly‐3‐hydroxyglutaryl‐CoA synthase (mHMG‐CoA‐S; 3.9 fold) in pigs fed clofibrate verses vehicle. Addition of etomoxir had no effects on the transcript abundances induced by clofibrate. Transcript abundance of targeted genes also increased as piglets aged, but the mRNA levels remained relatively constant for CPT I and mHMG‐CoA‐S in pigs after 4 d and for CPT II after 1 d. There was no interaction betwee...
This study evaluated the effects of supplementation of ARA on delta‐6‐desaturase (D6D) and delta‐... more This study evaluated the effects of supplementation of ARA on delta‐6‐desaturase (D6D) and delta‐5‐desaturase (D5D) mRNA abundance and synthesis of ARA in the intestine and liver. Day old pigs (n=96) were fed a milk based formula for 4, 8, and 16 d. Diets contained either no polyunsaturated fatty acids (0% ARA, negative control), 0.5% ARA, 2.5% ARA, 5% ARA or 5% eicosapentaenoic acid (EPA) of total fatty acids. A sow fed reference group (SRC n=18) also was included. The mRNA relative abundance increased differentially (diet x age interaction, P < 0.05) from d4 to d16 in pigs fed 0.5% (D6D‐55%, D5D‐66%) versus 5% (D6D‐60%, D5D‐64%) ARA diets in the intestine. Transcript abundance of D6D and D5D were not affected by diet in the liver (P>0.05), however, there was a precipitous decrease between birth and d4 (~5‐fold, P<0.05). To measure flux through the desaturase‐elongase pathway we incubated liver and intestinal mucosa with 13C‐linoleate(C18:2, n‐6) and traced its metabolism ...
A neonatal piglet model was used to study hepatic fatty acid metabolism during the early postnata... more A neonatal piglet model was used to study hepatic fatty acid metabolism during the early postnatal period. Hepatocytes were isolated from pigs at birth or after 24 h, in fed or unfed states (n = 4 pigs/group). Cells were incubated with 1 mmol/L [1-(14)C]-octanoate (C8) or -palmitate (C16) in the presence or absence of 1 mmol/L L-carnitine, carnitine plus tetradecylglycidic acid (TDGA; 10 mumol/L) or carnitine plus glucagon (0.5 microgram/L). Accumulation of radiolabel [nmol/(h. 10(6) cells)] in CO2 and acid-soluble products (ASP) was higher (3.5- and 4.5-fold, respectively) from C8 than from C16 (P < 0.0001). Glucagon, carnitine and TDGA had no effect on the oxidation of C8 (P > 0.1). Carnitine addition tended to increase C16 flux to ASP [from 5.3 to 7.6 nmol/(h. 10(6) cells); P < 0.1], whereas carnitine plus TDGA decreased flux (from 7.6 to 2.1; P < 0.001). Esterified products accounted for 70% of metabolized label in control C16 incubations; this was reduced to 62% by ...
We hypothesized that methylated fatty acids (e.g. 2-methylpentanoic acid (2MeP), phytanic or pris... more We hypothesized that methylated fatty acids (e.g. 2-methylpentanoic acid (2MeP), phytanic or pristanic acids) would provide anaplerotic carbon to the tricarboxylic acid (TCA) cycle and thereby enha...
American Journal of Physiology-Endocrinology and Metabolism, 1998
The current studies were performed to better understand the physiological relevance of acetate in... more The current studies were performed to better understand the physiological relevance of acetate in the poorly ketogenic piglet and to determine if endogenous acetogenesis rises with increased mitochondrial fatty acid β-oxidation, analogous to ketogenesis. Plasma acetate concentration values in newborn, fasted, or suckled piglets (230–343 μM) were at least 10-fold higher than the ketone bodies, a pattern opposite to that in 24- to 48-h suckled rats (77–175 μM). Employing continuous infusion techniques with sodium [3H]acetate tracer in fasting ∼40-h-old piglets, acetate rate of appearance (Ra) was found to be 34 ± 4 μmol ⋅ min−1⋅ kg body wt−1. This basal Rawas double that observed in animals coinfused with sodium [1-14C]hexanoate ( P < 0.001), despite active oxidation of the latter as determined by14CO2production. Active acetogenesis in vivo and relatively abundant acetate in piglet blood are consistent with the hypothesis that acetate plays an important physiological role in piglet...
Two studies were designed to determine the effects of supplementing diets with lipid sources of E... more Two studies were designed to determine the effects of supplementing diets with lipid sources of EFA (linoleic and α-linolenic acid) on sow milk composition to estimate the balance of EFA for sows nursing large litters. In Exp. 1, 30 sows, equally balanced by parity (1 and 3 to 5) and nursing 12 pigs, were fed diets supplemented with 6% animal-vegetable blend (A-V), 6% choice white grease (CWG), or a control diet without added lipid. Diets were corn-soybean meal based with 8% corn distiller dried grains with solubles and 6% wheat middlings and contained 3.25 g standardized ileal digestible Lys/Mcal ME. Sows fed lipid-supplemented diets secreted greater amounts of fat (P = 0.082; 499 and 559 g/d for control and lipid-added diets, respectively) than sows fed the control diet. The balance of EFA was computed as apparent ileal digestible intake of EFA minus the outflow of EFA in milk. For sows fed the control diet, the amount of linoleic acid secreted in milk was greater than the amount ...
An experiment was conducted to explore the nature of the radiolabel distribution in acid-soluble ... more An experiment was conducted to explore the nature of the radiolabel distribution in acid-soluble products (ASPs) resulting from the oxidation of [1-14C]C7:0 or C8:0 by isolated piglet hepatocytes. The differences between odd and even chain-length and the impacts of valproate and malonate upon the rate of β-oxidation and ASP characteristics were tested. A minor amount of fatty acid carboxyl carbon (⩽ 10% of organic acids identified by radio-HPLC) accumulated in ketone bodies regardless of chain-length or inhibitor used. In all cases, acetate represented the major reservoir of carboxyl carbon, accounting for 60–70% of radiolabel in identified organic acids. Cells given [1-14C]C7:0 accumulated 85% more carboxyl carbon in Krebs cycle intermediates when compared with C8:0, while accumulation in acetate was unaffected. The results are consistent with the hypothesis that anaplerosis from odd-carbon fatty acids affects the oxidative fate of fatty acid carbon. The piglet appears unique in th...
Utilization of energy-dense lipid fuels is critical to the rapid development and growth of neonat... more Utilization of energy-dense lipid fuels is critical to the rapid development and growth of neonates. To increase efficiency of milk fat utilization by newborn pigs, the effect of clofibrate on in vivo and in vitro long-chain fatty acid (LCFA) oxidation was evaluated. Newborn male pigs were administered 5 mL of vehicle (2% Tween 80) with or without clofibrate (75 mg/kg body weight) once daily via i.g. gavage for 4 d. Total LCFA oxidative capacity was measured in respiration chambers after gastric infusion (n = 5 per treatment) with isoenergetic amounts of [1-(14)C]triglycerides (TGs), either oleic acid (18:1n-9) TG [3.02 mmol/kg body weight (BW)(0.75)] or erucic acid (22:1n-9) TG (2.46 mmol/kg BW(0.75)). Total expired (14)CO2 was collected and quantified at 20-min intervals over 24 h. Hepatic in vitro LCFA oxidation was determined simultaneously using [1-(14)C]oleic acid and erucic acid substrates. The in vivo 24-h accumulative [1-(14)C]TG oxidation (percentage of energy intake/kg BW...
To investigate the effect of protein-energy malnutrition on intestinal barrier function during ro... more To investigate the effect of protein-energy malnutrition on intestinal barrier function during rotavirus enteritis in a piglet model. Newborn piglets were allotted at day 4 of age to the following treatments: (1) full-strength formula (FSF)/noninfected; (2) FSF/rotavirus infected; (3) half-strength formula (HSF)/noninfected; or (4) HSF/rotavirus infected. After one day of adjustment to the feeding rates, pigs were infected with rotavirus and acute effects on growth and diarrhea were monitored for 3 d and jejunal samples were collected for Ussing-chamber analyses. Piglets that were malnourished or infected had lower body weights on days 2 and 3 post-infection (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). Three days post-infection, marked diarrhea and weight loss were accompanied by sharp reductions in villus height (59%) and lactase activity (91%) and increased crypt depth (21%) in infected compared with non-infected pigs (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). Malnutrition also increased crypt depth (21%) compared to full-fed piglets. Villus:crypt ratio was reduced (67%) with viral infection. There was a trend for reduction in transepithelial electrical resistance with rotavirus infection and malnutrition (P = 0.1). (3)H-mannitol flux was significantly increased (50%; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) in rotavirus-infected piglets compared to non-infected piglets, but there was no effect of nutritional status. Furthermore, rotavirus infection reduced localization of the tight junction protein, occludin, in the cell membrane and increased localization in the cytosol. Overall, malnutrition had no additive effects to rotavirus infection on intestinal barrier function at day 3 post-infection in a neonatal piglet model.
Tryptophan (Trp), the rate-limiting substrate of serotonin [5-hydroxytryptoamine (5-HT)] synthesi... more Tryptophan (Trp), the rate-limiting substrate of serotonin [5-hydroxytryptoamine (5-HT)] synthesis in the brain, competes with large neutral amino acids (LNAA) to cross the blood-brain barrier. This study was designed to evaluate the effect of L-Trp supplementation on nursery pigs experiencing social-mixing stress and fed diets varying in LNAA concentrations. Forty-eight individually housed barrows at 6 wk of age were randomly allotted to 4 dietary treatments based on a 2 × 2 factorial arrangement, with L-Trp supplementation (0 or 0.6%) and LNAA concentrations (4.5 or 3.8%) as the 2 main factors. Pigs were fed the diets for 7 d. On d 4, pigs within a treatment were paired in a new pen to create social-mixing stress and behavior was recorded for 24 h. Body weight was measured on d 0, 4, 5, and 7. Saliva and blood were collected on d 4 and 7. On d 7, pigs were killed to obtain hypothalami. During the entire period excluding the mixing day (d 5), L-Trp supplementation improved (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) feed efficiency of pigs and lowering the LNAA further enhanced (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) the effects of L-Trp. Supplementation of 0.6% L-Trp increased (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) hypothalamic 5-HT and 5-hydroxyindoleacetic acid. The salivary cortisol concentration was reduced (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) by lowering the LNAA. Collectively, lowering the LNAA further enhanced the improvement of feed efficiency by L-Trp supplementation of nursery pigs under social-mixing stress in association with reduced stress hormones, indicating that reducing LNAA in the diet can facilitate the effect of L-Trp on the stress response of pigs.
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