Skip to main content
NCBI home page
Journal of Animal Science logoLink to Journal of Animal Science
. 2019 Jun 28;97(8):3354–3368. doi: 10.1093/jas/skz204

Postprandial insulin and nutrient concentrations in lipopolysaccharide-challenged growing pigs reared in thermoneutral and high ambient temperatures1

Paulo Henrique Reis Furtado Campos 1,✉, Elodie Merlot 2, David Renaudeau 2, Jean Noblet 2, Nathalie Le Floc’h 2
PMCID: PMC6667261  PMID: 31250878

Abstract

The aim of this study was to evaluate the associated effects of ambient temperature and inflammation caused by repeated administration of Escherichia coli lipopolysaccharide (LPS) on insulin, energy, and AA metabolism. Twenty-eight pigs were assigned to one of the two thermal conditions: thermoneutral (24 °C) or high ambient temperature (30 °C). The experimental period lasted 17 d, which was divided into a 7-d period without LPS (days −7 to −1), and a subsequent 10-d LPS period (days 1 to 10) in which pigs were administered 5 repeated injections of LPS at 2-d intervals. Postprandial profiles of plasma insulin and nutrients were evaluated through serial blood samples taken on days −4 (P0), 4 (P1), and 8 (P2). Before the LPS-challenge (P0), postprandial concentrations of glucose, lactate, Gln, Ile, Leu, Phe, Tyr, and Val were greater in pigs kept at 24 °C than at 30 °C (P < 0.05). In contrast, Arg, Asp, Gly, His, and Met postprandial concentrations at P0 were lower at 24 °C than at 30 °C (P < 0.05). At both 24 and 30 °C conditions, pigs had greater postprandial concentrations of insulin (P < 0.01) and lower concentrations of NEFA (P < 0.01) and α-amino nitrogen (P < 0.05) at P1 and P2 than at P0. Compared with P0, postprandial concentrations of glucose were greater (P < 0.05) at P1 in pigs kept at 24 °C, and at P1 and P2 in pigs kept at 30 °C. At both ambient temperatures, pigs had lower (P < 0.05) postprandial concentrations of Ala, Gly, His, Ile, Leu, Pro, Ser, Thr, Trp, and Val at P1 and P2 than at P0. Arginine postprandial concentration at P1 was lower than at P0 in pigs kept at 24 °C (P < 0.05), whereas no difference was observed in pigs at 30 °C. Relative to P0, Gln and Tyr concentrations were lower at P1 and P2 in pigs kept at 24 °C (P < 0.01), whereas lower Gln concentration was observed only at P2 (P < 0.01) and lower Tyr only at P1 (P < 0.01) in pigs kept at 30 °C. Our study shows a hyperglycemic and hyperinsulinemic state in LPS-challenged pigs and a greater magnitude of this response in pigs kept at 30 °C. Furthermore, LPS caused important changes in BCAA, His, Thr, and Trp profiles, suggesting the role these AA in supporting the inflammatory response. Finally, our results suggest that LPS-induced effects on postprandial profiles of specific AA (Arg, Gln, Phe, and Tyr) may be modulated by ambient temperature.

Keywords: amino acids, heat stress, inflammation, LPS, meal test, metabolites

INTRODUCTION

Intensification of livestock production in hot climate areas and global warming will contribute to a greater exposure of animals to heat stress conditions characterized by ambient temperatures above 25 °C for growing–finishing pigs (Renaudeau et al., 2007). In addition, global warming has been associated with increased number and dissemination of disease vectors and pathogens besides increased incidence of emerging diseases (Kimaro and Chibinga, 2013). Therefore, pig production will be more and more exposed to heat stress and immune challenges. Heat stress results in decreased voluntary feed intake and growth, lower circulating levels of thyroid hormones (Campos et al., 2014c), and consequent lower metabolic heat production (Campos et al., 2014a). Besides, shorter intestinal villus, reduced intestinal integrity and increased circulating endotoxin (Pearce et al., 2013b,c), and decreased abundance and activity of intestinal AA transporters (Morales et al., 2014) have been described in heat-stressed pigs. On the other hand, sanitary challenges decrease voluntary feed intake and growth (Pastorelli et al., 2012) and activate the immune system resulting in increased energy expenditure (Campos et al., 2014a) and demand for specific AA (Le Floc’h et al., 2018). Much of the published work has focused on the evaluation of pig responses to high ambient temperatures or sanitary challenges separately; consequently, little is known on their associated effects. In addition, studies have reported a modulatory effect of ambient temperature on pig responses to an inflammatory challenge (Campos et al., 2014a,b). Given the impact of high ambient temperature and inflammation on nutrients intake, and the crucial roles of AA in regulating immunity, anti-oxidation, and intestinal integrity and function; this study aims at evaluating the associated effects of ambient temperature and inflammation caused by repeated administration of LPS on insulin, energy, and AA metabolism.

MATERIALS AND METHODS

The experiment was conducted in accordance with the French legislation on animal experimentation and approved by the Regional Ethics Committee on Animal Experimentation of Rennes, France (authorization: R-2012-NLF-02).

Animals, Housing, and Diet

The study aimed at investigating the effects of ambient temperature on postprandial plasma insulin and metabolites in growing pigs subjected to repeated administrations of LPS. It included a subset of 28 Piétrain x (Landrace x Large White) male and female growing pigs (Campos et al., 2014b) originated from the experimental herd of INRA Saint-Gilles, France (INRA UMR PEGASE). At approximately 35 kg BW, pigs were assigned, on the basis of their body weight and sex, to one of the two thermal conditions: thermoneutral (TN, 24 °C) or high ambient temperature (HT, 30 °C). Each pig was surgically fitted with a jugular catheter, according to the procedure previously described by Campos et al. (2014c), and transferred to temperature-controlled rooms (TN or HT), according to their allocation. In each room, pigs were housed in individual metal-slatted pens (TN: 0.85 × 1.30 m; HT: 0.70 × 2.30 m) equipped with a feed dispenser and a nipple drinker. Pigs had free access to water and were fed ad libitum a cereal and soybean meal-based standard diet (Table 1). Photoperiod was fixed to 12 h of artificial light (0800 to 2000 h) and 12 h of darkness.

Table 1.

Ingredients and chemical composition of the diet (as-fed basis)

Item
Ingredients, %
 Wheat 26.2
 Barley 25.5
 Corn 16.0
 Soybean meal 19.0
 Wheat bran 5.0
 Molasses 3.0
 Vegetable oil 2.0
 Calcium carbonate 1.29
 Dicalcium phosphate 0.50
 Salt 0.45
 L-Lys HCl 0.33
 DL-Met 0.04
 L-Thr 0.03
 Vitamins and trace minerals mixture1 5.0
Analyzed composition and nutritional value2
 CP, % 17.87
 Ash, % 5.14
 Ether extract, % 3.33
 Starch, % 39.62
 Crude fiber, % 3.03
 NDF, % 12.94
 ADF, % 3.90
 ADL, % 0.54
 GE, MJ/kg 15.61
 ME3, MJ/kg 12.51
 NE3, MJ/kg 9.36
Amino acids (total basis), %
 Lys 1.31
 Thr 0.89
 Met 0.36
 Cys 0.40
 Arg 1.47
 His 0.59
 Ile 0.97
 Leu 1.71
 Phe 1.13
 Tyr 0.89
 Val 1.16
 Ala 1.05
 Gly 1.02
 Gln 4.75
 Asn 2.18
 Pro 1.30
 Ser 1.16
Open in a new tab

1Supplied per kilogram (as-fed basis) of diet: vitamin A, 5,000 IU; vitamin D3, 1,000 IU; vitamin E, 20 IU; menadione, 2 mg; thiamine, 2 mg; riboflavin, 4 mg; niacin, 15 mg; pantothenic acid, 10 mg; pyridoxine, 1 mg;biotin, 0.2 mg; folic acid, 1 mg; cyanocobalamin, 0.02 mg; choline chloride, 500 mg; Fe, 80 mg as ferrous carbonate; Cu, 10 mg as copper sulfate; Zn, 100 mg as zinc oxide; Mn, 37 mg as manganous oxide; I, 0.2 mg ascalcium iodate; Se, 0.2 mg as sodium selenite; and Co, 0.1 mg as cobalt sulfate.

2Adjusted for 88.0% DM.

3Values calculated according to Sauvant et al. (2002).

Pigs remained in the temperature-controlled rooms during a 31-d period that consisted in a 14-d adaptation and a subsequent 17-d experimental period. The ambient temperature (Ta) of the TN room was maintained at 24 °C during the whole adaptation and experimental periods. The Ta of the HT room was maintained at 24 °C during the first 5 d of the adaptation period and thereafter at 30 °C. This temperature transition from 24 to 30 °C occurred gradually over 3 successive days at a constant rate of +2 °C per day. The exposure of pigs to HT during 1 wk was sufficient to acclimate the animals according to a previous study showing that adaptation to an ambient temperature of 30 °C required 3 to 4 d (Campos et al., 2014c). Ambient temperature in each room was recorded every 5 min using a data logger (EL-USB-2+, DATAQ Instruments) located in the middle of the room. Relative humidity was not controlled (i.e., was not kept constant) but was recorded using the same data logger as for ambient temperature.

The experimental period was divided into 2 successive periods: a first 7-d period before (from days −7 to −1) and a 10-d period during (from days 1 to 10) the inflammatory challenge that consisted in repeated injections of LPS (O55:B5, Sigma-Aldrich; Saint Quentin Fallavier, France) to induce a chronic inflammatory response. The LPS injections were administrated at 11:00 h on days 1 (LPS1), 3 (LPS2), 5 (LPS3), 7 (LPS4), and 9 (LPS5) following a procedure adapted from Rakhshandeh et al. (2012). The initial dose of 30 µg/kg of body weight was increased by 12% at each subsequent injection to circumvent adaptive endotoxin resistance to the repeated inflammatory stimuli. The first to fourth LPS injections were performed intravenously via the catheter, with the fifth one given intramuscularly into the neck muscle to avoid a transient malaise observed in some pigs during LPS4 administration. All pigs were euthanized 24 h after the LPS5 administration by a letal injection of T61 (MSD Santé Animale, Beaucouzé, France) through the catheter.

Postprandial Profiles of Plasma Insulin and Nutrient Concentrations

Postprandial profiles of plasma glucose, insulin, lactate, nonesterified fatty acids (NEFA), urea, α-amino acids, and AA (Ala, Arg, Asn, Asp, Glu, Gln, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, Val) were evaluated before LPS administration (day −4, P0), the day after LPS2 administration (day 4, P1), and the day after LPS4 administration (day 8, P2); P1 and P2 days were selected to assess short- and medium-term phases of the LPS challenge, respectively. On P0, P1, and P2 days, and after being fasted overnight, each pig was offered 300 g of the standard diet at 0800 h. This meal size was determined to ensure that all pigs ate their meal in less than 10 min (Le Floc’h et al., 2017). Concomitantly, blood samples (4 mL) were withdrawn through the catheter at 0, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 210, and 240 min relative to the meal delivery (time 0) to asses insulin and nutrients postprandial concentrations. Blood was collected on lithium heparin anticoagulant tubes immediately placed on ice and then centrifuged (2,800 × g) for 15 min at 4 °C. Plasma was then stored at −20 °C until analyses.

Biochemical Analyses

Insulin was determined using a commercial immunoassay on an automated analyzer (ST AIA-PACK IRI methodology and AIA-1800 apparatus, TOSOH Bioscience, Tokyo, Japan). Intra- and inter-assay for insulin were less than 2.3% and 4.6%, respectively. Automated enzymatic methods using a multianalyzer apparatus (Konelab20i, Thermo Electron Corporation, Cergy, France) were used to determine plasma concentrations of glucose, lactate, and urea (reference 61269, 61192, and 61974, respectively, bioMérieux, Marcy l’Etoile, France), NEFA (NEFA kit, Wako Chemicals, Neuss Germany), and α-amino acids (Chacornac et al., 1993). Plasma AA concentrations were determined by an ultra-performance liquid chromatography (UPLC) system (Waters Acquity Ultra Performance LC, Waters, Milford, MA) coupled to 2 detectors (Acquity Tunable UV detector and Mass SQD detector; Waters, Milford, MA) after derivatization of samples using the AccQ Tag Ultra method (MassTrak AAA;Waters, Milford, MA). Norvaline (Sigma–Aldrich, Saint Quentin Fallavier, France) was used as an internal standard.

Data Analysis and Statistics

Average postprandial plasma concentrations of insulin and nutrients included the fasted concentration and were analyzed separately for periods before (P0) and during (P1 and P2) the LPS challenge. The presence of outliers was evaluated through the residual analysis of data and by daily records of anomalies. The BoxCox and Cramer-von Mises tests were used to verify homogeneity of the variances and normality of the studentized residuals, respectively. Within P0, data were analyzed using a general linear model (GLM procedure of SAS) that included the fixed effects of Ta (TN or HT), time sampling (0 to 240 after the meal delivery), and their interaction. Within the LPS challenge, data were analyzed using the linear mixed model and included the fixed effects of Ta, phase of the LPS challenge (P1 or P2), time sampling, and their interactions. The phase of the LPS challenge was specified as a repeated effect in the mixed model and a compound symmetry covariance structure was used to account for animal effect over the phases. In a second approach, daily means measured during the LPS challenge (i.e., P1 and P2 values) were compared with P0 using the contrast statement of the MIXED procedure. In all analyses, the animal was considered as random effect and the adjusted means were compared using the Bonferroni test. The effects were considered as significant if P < 0.05.

RESULTS

The model of repeated injections of increasing amounts of LPS used in the study successfully induced a chronic inflammatory state, which was evidenced by loss of appetite, increased rectal temperature (RT), and haptoglobin circulating levels (Hp) during the LPS challenge (Campos et al., 2014b). For instance, before the LPS challenge, ADFI, ADG, RT, and Hp of the subset of pigs used in the current study was 1,744 g/d, 849 g/d, 39.0 °C, and 1.41 mg/mL in TN pigs; and 1,556 g/d, 647 g/d, 40.0 °C, and 0.99 mg/mL in HT pigs. During the LPS challenge, the respective values were 1,195 g/d, 310 g/d, 40.0 °C, and 2.52 mg/mL in TN pigs; and 1,282 g/d, 648 g/d, 40.7 °C, and 2.04 mg/mL in HT pigs. On P0, P1, and P2 days, all pigs consumed their 300-g meal within less than 10 min and the jugular catheters worked properly during the entire experimental period.

Effects of Ambient Temperature and LPS on Average Postprandial Concentrations of Insulin and Metabolites

Plasma postprandial concentrations of insulin and metabolites are presented in Table 2. Before the LPS challenge, HT pigs had lower (P < 0.01) glucose and lactate, and greater (P < 0.01) α-amino nitrogen average postprandial concentrations than TN pigs. At P0, ambient temperature did not affect insulin, NEFA, and urea postprandial concentrations.

Table 2.

Plasma insulin and metabolites average postprandial concentrations in pigs kept at 24 and 30 °C before (P0) and during short- (P1) and medium-term (P2) phases of LPS challenge (least square means of 14 pigs per ambient temperature)1

Before LPS P-value3 LPS challenge P-value4
Item P0 RSD2 Ta P1 P2 RSD2 Ta P Ta × P
Insulin, µU/mL
 24 °C 26.9 24 0.73 45.0** 36.7** 23 0.09 <0.001 0.69
 30 °C 26.1 51.6†† 44.7††
Glucose, mg/L
 24 °C 1210 148 <0.001 1322** 1220 199 0.84 <0.001 0.03
 30 °C 1149 1283†† 1244†
Lactate, µmol/L
 24 °C 1404 478 <0.001 1229** 1221** 241 0.10 0.02 0.05
 30 °C 1132 1183 1106
NEFA, µmol/L
 24 °C 282 226 0.33 179** 153** 89 0.12 0.04 0.03
 30 °C 305 186†† 187††
α-amino nitrogen, mg/L
 24°C 689 92 <0.001 668* 666* 71 0.40 0.17 0.08
 30°C 724 645†† 660††
Urea, mg/L
 24°C 279 82 0.84 253** 260** 39 0.52 <0.001 <0.001
 s30°C 273 245†† 286
Open in a new tab

1The LPS challenge consisted of 5 successive injections of Escherichia coli lipopolysaccharide performed at 48-h intervals each. P0 corresponds to the time point before the LPS challenge, and P1 and P2 corresponded to the days after the second and fourth LPS injection, respectively. Average plasma postprandial concentrations measured 0, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 210, and 240 min relative to a 300-g meal delivery at time 0 (see Figure 1 for postprandial profiles). Within each ambient temperature, linear contrasts were generated to compare P1 and P2 values to P0, using the contrast statement of the MIXED procedure. Within 24 °C, *P < 0.05, **P < 0.01. Within 30 °C, †P < 0.05, ††P < 0.01.

2Residual SD.

3Within P0, data were analyzed using a general linear model including the fixed effects of ambient temperature (Ta), time sampling (0 to 240 min after the meal delivery), and their interaction as fixed effects.

4Within LPS challenge, data were analyzed using a linear mixed model including the effect of ambient temperature (Ta), phase of the LPS challenge (P), time sampling (0 to 240 after the meal delivery), and their interaction as fixed effects. The phase of the LPS challenge was specified as a repeated effect.

Figure 1.

Figure 1.

Open in a new tab

Postprandial profiles of insulin and metabolites before (P0) and during short- (P1) and medium-term (P2) phases of LPS challenge in pigs kept at 24 and 30 °C. The LPS challenge consisted of 5 successive injections of Escherichia coli lipopolysaccharide performed at 48-h intervals each. P0 corresponds to the time point before the LPS challenge, and P1 and P2 corresponded to the days after the second and fourth LPS injection, respectively. Each point is the least squares mean of 14 pigs.

At both TN and HT conditions, pigs had greater postprandial concentrations of insulin (P < 0.01) and lower postprandial concentrations of NEFA (P < 0.01) and α-amino nitrogen (P < 0.05) at P1 and P2 than at P0. Postprandial concentrations of glucose were greater than at P0 at P1 in pigs kept at TN (P < 0.01) and at P1 (P < 0.01) and P2 (P < 0.05) in pigs kept at HT. Lactate postprandial concentrations at P1 and P2 were lower than at P0 in pigs kept at TN (P < 0.01), whereas no difference was observed in HT pigs. Relative to P0, urea postprandial concentrations were lower at P1 and P2 in pigs kept at TN (P < 0.01) and only at P1 in pigs kept at HT (P < 0.01).

Effects of Ambient Temperature and LPS on Average Postprandial Concentrations of Amino Acids

Plasma postprandial concentrations of free indispensable AA are presented in Table 3. At P0, pigs housed at HT had greater postprandial concentrations of Arg (P < 0.01), His (P = 0.02), and Met (P < 0.01), and lower (P < 0.01) postprandial concentrations of Ile, Leu, Phe, and Val than pigs kept at TN. Ambient temperature did not affect Lys, Thr, and Trp postprandial concentrations at P0. At both TN and HT conditions, pigs had lower (P < 0.01) postprandial concentrations of His, Ile, Leu, Thr, Trp, and Val at P1 and P2 than at P0. Arginine postprandial concentration at P1 was lower than at P0 in pigs kept at HT (P < 0.05), whereas no difference was observed in TN pigs. Compared with P0, postprandial concentrations of Lys were lower at P1 (P < 0.01) and greater at P2 (P < 0.01) in pigs kept at TN, and greater at P2 in pigs kept at HT (P < 0.01). Postprandial concentrations of Met were not affected by the LPS challenge neither in TN nor in HT pigs. Pigs kept at TN had lower concentrations of Phe at P1 and P2 than at P0, whereas no difference was observed in pigs kept at HT.

Table 3.

Postprandial plasma concentration of free indispensable AA in pigs kept at 24 and 30 °C before (P0) and during short- (P1) and medium-term (P2) phases of LPS challenge (least square means of 14 pigs per ambient temperature)1

Before LPS P-value3 LPS challenge P-value4
Item P0 RSD2 Ta P1 P2 RSD2 Ta P Ta × P
Arg, µmol/L
 24 °C 116 28 <0.001 113 129 20 0.95 <0.001 0.02
 30 °C 134 116† 125
His, µmol/L
 24 °C 84.1 13.8 0.02 72.4** 76.8** 9.3 0.79 <0.001 0.78
 30 °C 87.4 71.3†† 76.1††
Ile, µmol/L
 24 °C 161 26 <0.001 131** 120** 15 0.22 <0.01 <0.001
 30 °C 146 117†† 121††
Leu, µmol/L
 24 °C 225 41 <0.001 177** 184** 22 0.59 <0.001 <0.001
 30 °C 207 165†† 187††
Lys, µmol/L
 24 °C 155 51 0.11 136** 171** 28 0.51 <0.001 0.04
 30 °C 147 137 180††
Met, µmol/L
 24 °C 31.9 7.1 <0.01 30.8 30.6 5.2 0.56 0.19 0.08
 30 °C 33.8 31.2 32.3
Phe, µmol/L
 24 °C 116 15 <0.001 101** 102** 12 0.16 0.92 0.55
 30 °C 109 106 106
Thr, µmol/L
 24 °C 147 31 0.06 103** 114** 17 0.72 <0.001 0.01
 30 °C 140 102†† 119††
Trp, µmol/L
 24 °C 68.8 9.7 0.09 54.1** 51.9** 6.9 0.39 0.88 <0.001
 30 °C 70.5 54.0†† 56.1††
Val, µmol/L
 24 °C 356 49 <0.001 286** 284** 29 0.92 <0.001 <0.001
 30 °C 324 264†† 304††
Open in a new tab

1The LPS challenge consisted of 5 successive injections of Escherichia coli lipopolysaccharide performed at 48-h intervals each. P0 corresponds to the time point before the LPS challenge, and P1 and P2 corresponded to the days after the second and fourth LPS injection, respectively. Average plasma postprandial concentrations measured 0, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 210, and 240 min relative to a 300-g meal delivery at time 0 (see Figure 2 for postprandial profiles). Within each ambient temperature, linear contrasts were generated to compare P1 and P2 values to P0, using the contrast statement of the MIXED procedure. Within 24 °C, *P < 0.05, **P < 0.01. Within 30 °C, †P < 0.05, ††P < 0.01.

2Residual SD.

3Within P0, data were analyzed using a general linear model including the fixed effects of ambient temperature (Ta), time sampling (0 to 240 min after the meal delivery), and their interaction as fixed effects.

4Within LPS challenge, data were analyzed using a linear mixed model including the effect of ambient temperature (Ta), phase of the LPS challenge (P), time sampling (0 to 240 after the meal delivery), and their interaction as fixed effects. The phase of the LPS challenge was specified as a repeated effect.

Figure 2.

Figure 2.

Open in a new tab

Postprandial profiles of free indispensable amino acids before (P0) and during short- (P1) and medium-term (P2) phases of LPS challenge in pigs kept at 24 and 30 °C. The LPS challenge consisted of 5 successive injections of Escherichia coli lipopolysaccharide performed at 48-h intervals each. P0 corresponds to the time point before the LPS challenge, and P1 and P2 corresponded to the days after the second and fourth LPS injection, respectively. Each point is the least squares mean of 14 pigs.

Regarding free dispensable AA (Table 4), at P0, pigs kept at HT had greater (P < 0.01) postprandial concentrations of Asp and Gly, and lower (P < 0.01) concentrations of Gln and Tyr than pigs kept at TN. At both TN and HT conditions, pigs had lower postprandial concentrations of Ala (P < 0.05), Gly (P < 0.05), Pro (P < 0.01), and Ser (P < 0.01) at P1 and P2 than at P0. Postprandial concentrations of Asn at P1 were lower than at P0 in both thermal conditions (P < 0.05). Compared with P0, postprandial concentrations of Asp were greater at P1 (P < 0.01) and lower at P2 (P < 0.01) in pigs kept at TN, and lower at both P1 and P2 in pigs kept at HT (P < 0.01). Postprandial concentrations of Glu were greater than at P0 at P1 and P2 in pigs kept at TN (P < 0.01), and at P1 in pigs kept at HT (P < 0.01). Glutamine concentrations were lower than at P0 at P1 and P2 in pigs kept at TN (P < 0.01), and at P2 in pigs kept at HT (P < 0.01). Relative to P0, Tyr postprandial concentrations were lower at P1 and P2 in pigs kept at TN (P < 0.01), and at P1 in pigs kept at HT (P < 0.01).

Table 4.

Postprandial plasma concentration of free dispensable AA in pigs kept at 24 and 30 °C before (P0) and during short- (P1) and medium-term (P2) phases of LPS challenge (least square means of 14 pigs per ambient temperature)1

Before LPS P-value3 LPS challenge P-value4
Item P0 RSD2 Ta2 P1 P2 RSD2 Ta P Ta × P
Ala, µmol/L
 24 °C 448 77 0.13 409* 410* 53 0.17 0.73 0.57
 30 °C 460 386†† 390††
Asn, µmol/L
 24 °C 97 27 0.17 86.5* 98.4 17.9 0.49 <0.001 0.07
 30 °C 101 80.2†† 96.8
Asp, µmol/L
 24 °C 14.6 3.7 <0.01 16.9** 12.5** 4.0 0.86 <0.001 <0.001
 30 °C 18.3 15.4†† 13.6††
Glu, µmol/L
 24 °C 118 35 0.22 189** 132** 34 0.04 <0.001 <0.001
 30 °C 123 152†† 118
Gln, µmol/L
 24 °C 501 91 <0.001 454** 437** 64 0.07 <0.001 <0.001
 30 °C 457 429 377††
Gly, µmol/L
 24 °C 807 200 <0.001 769* 711** 79 0.08 <0.001 0.21
 30 °C 898 700†† 655††
Pro, µmol/L
 24 °C 272 46 0.19 225** 228** 26 0.06 <0.001 <0.001
 30 °C 279 202†† 225††
Ser, µmol/L
 24 °C 178 38 0.55 150** 144** 16 0.34 <0.001 0.87
 30 °C 176 144†† 138††
Tyr, µmol/L
 24 °C 88.9 16.7 <0.001 55.6** 70.6** 12.4 0.14 <0.001 <0.001
 30 °C 81.5 55.8†† 78.2
Open in a new tab

1The LPS challenge consisted of 5 successive injections of Escherichia coli lipopolysaccharide performed at 48-h intervals each. P0 corresponds to the time point before the LPS challenge, and P1 and P2 corresponded to the days after the second and fourth LPS injection, respectively. Average plasma postprandial concentrations measured 0, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 210, and 240 min relative to a 300-g meal delivery at time 0 (see Figure 3 for postprandial profiles). Within each ambient temperature, linear contrasts were generated to compare P1 and P2 values to P0, using the contrast statement of the MIXED procedure. Within 24 °C, *P < 0.05, **P < 0.01. Within 30 °C, †P < 0.05, ††P < 0.01.

2Residual SD.

3Within P0, data were analyzed using a general linear model including the fixed effects of ambient temperature (Ta), time sampling (0 to 240 min after the meal delivery), and their interaction as fixed effects.

4Within LPS challenge, data were analyzed using a linear mixed model including the effect of ambient temperature (Ta), phase of the LPS challenge (P), time sampling (0 to 240 after the meal delivery), and their interaction as fixed effects. The phase of the LPS challenge was specified as a repeated effect.

Figure 3.

Figure 3.

Open in a new tab

Postprandial profiles of free dispensable amino acids before (P0) and during short- (P1) and medium-term (P2) phases of LPS challenge in pigs kept at 24 and 30 °C. The LPS challenge consisted of 5 successive injections of Escherichia coli lipopolysaccharide performed at 48-h intervals each. P0 corresponds to the time point before the LPS challenge, and P1 and P2 corresponded to the days after the second and fourth LPS injection, respectively. Each point is the least squares mean of 14 pigs.

DISCUSSION

Postprandial nutrients plasma appearance and utilization was investigated after a meal test in which overnight-fasted pigs were offered and ingested a 300 g of diet within less than 10 min after its delivery. Therefore, differences in plasma insulin and nutrients metabolites postprandial profiles are mainly explained by differences in endocrine status, nutrients metabolism, and energy and AA requirements.

Effects of Ambient Temperature on Postprandial Concentrations of Nutrients in Healthy Growing Pigs

Before the LPS-challenge, pigs were in overt good health and adapted to the experimental conditions. Therefore, any differences in postprandial profiles of nutrients between pigs kept at 24 and 30 °C were associated with an effect of ambient temperature. In our study, despite similar postprandial concentrations of insulin between pigs kept at 24 and 30 °C, glucose postprandial concentrations were lower in pigs housed at 30 °C. These results corroborate with those demonstrating that pigs exposed to high ambient temperatures have increased sensitivity to insulin (Sanz Fernandez et al., 2015b) resulting in increased whole-body glucose utilization. Thus, greater glucose utilization in response to high ambient temperatures might be an specific adaptative response. For instance, it might result from an increased reliance on glucose as energetic source in hot conditions (Sanz Fernandez et al., 2015b) and/or even associated with a greater use of glucose to support heat-acclimation processes such as the synthesis of heat shock proteins (Li et al., 2006; Rhoads et al., 2013). The absence of ambient temperature effect on NEFA postprandial concentrations in the current study supports previous indications that pigs do not mobilize body fat reserves in response to high ambient temperature (Sanz Fernandez et al., 2015a,b), despite the usual reduction in feed intake and growth in such conditions. This response being partially explained by the antilipolytic action of insulin on adipose tissue and by a high ambient temperature-induced decrease in the lipoprotein lipase activity (Pearce at al. 2013a).

In the present study, pigs kept at 30 °C had greater postprandial concentrations of α-amino nitrogen. It might be a consequence of a lower whole-body uptake of amino acids for protein accretion and other biological functions since pigs kept at 30 °C have decreased body weight gain (−212 g/d; Campos et al., 2014b) and metabolic rate (Campos et al., 2014a) than those at 24 °C. In addition, postprandial concentrations of Arg, Asp, His, Met, and Gly were greater at high than at thermoneutral ambient temperature. Arginine has multifaceted properties including serving as precursor for the synthesis of polyamines (putrescine, spermidine, and spermine) which are organic compounds derived from ornithine by the arginase pathway. Polyamines are required for DNA synthesis and then related to protein synthesis regulation and cell function and differentiation (Wang et al., 2003; Wu et al., 2013). Methionine is also a versatile amino acid crucial for intestinal mucosa development and integrity (Chen et al., 2014; Shen et al., 2014), protein synthesis, and the activated form of Met S‐adenosylmethionine is essential for DNA and protein methylation and the synthesis of spermidine and spermine (Li et al., 2007; Liu et al., 2017). Aspartate is a nonessential amino acid serving as energy substrate and precursor for the synthesis of other amino acids such as Met, Thr, Ile, and Lys (Liu et al., 2017). In regard to the biological functions of the above-mentioned amino acids, their greater circulating levels at high ambient temperatures might be explained by an decreased whole-body demand for these compounds and decreased interconversion of these amino acids into other substances acids as a result of the decreased metabolic rate and growth (Campos et al., 2014a,c) of pigs exposed to high ambient temperatures.

In contrast, postprandial concentrations of Ile, Leu, Phe, Val, Gln, and Tyr were lower in pigs kept at high ambient temperature. These findings suggest that high ambient temperature may specifically affect the metabolism and/or absorption of these amino acids. A decrease in intestinal villus height (Yu et al., 2010; Pearce et al., 2013c) and/or even decreased abundance and activity of amino acids transporters in the intestinal mucosa have been described (Morales et al., 2014) in response to high ambient temperature exposure. In agreement to our findings, serum postprandial concentrations of Leu and Phe measured 2.5 h after a morning meal were decreased in pigs exposed to natural high ambient temperatures (24 to 38 °C) when compared with their counterparts maintained at controlled thermoneutral conditions (24 °C), which was associated with a reduced abundance or activity of their respective amino acid transporters (Morales et al., 2016). Because of no evidence of high ambient temperature effect on Leu, Gln, and Tyr intestinal transporters (Morales et al., 2016), the lower postprandial concentrations of these amino acids in pigs kept at 30 °C in the current study were primary explained by a specific metabolic demand. Indeed, Gln (along with Glu) is a major substrate for energy supply, gluconeogenesis, as well as precursor of other amino acids (Arg, Pro, Orn) and glutathione (Watford, 2008) in the gut. Therefore, because high ambient temperature decreases voluntary feed intake (Renaudeau et al., 2011) and compromises intestinal development and integrity (Pearce et al., 2013b,c), a greater amount of Gln might be necessary to serve as energy substrate and to support enterocytes and intestinal mucosal integrity and function (Wu et al., 2012; Liu et al., 2017). In regard to Tyr postprandial concentrations, a greater demand of this amino in high ambient temperature conditions might be related to the modulatory effect of Tyr through the Tyr-kinase on heat shock proteins expression which, in turn, is increased in response to high ambient temperature (Pearce et al., 2013c; Rhoads et al., 2013). These proteins act preserving cells and tissues integrity in response to stressful stimuli such as heat stress (Heidemann and Glibetic, 2005).

From these results, it can be suggested that besides the modulatory effects of ambient temperature on feed intake, protein and lipid deposition, and endocrine and thermoregulatory responses (Campos et al., 2017), pigs exposure to high ambient temperature also results in increased metabolic demand for specific amino acids to protect and adapt the organism to heat stress, and in a putative decrease in the abundance and/or activity of some amino acid transporters in the intestinal mucosa which leads to lower postprandial concentrations of amino acids.

A LPS-Induced Inflammatory Challenge Alters Postprandial Concentrations of Nutrients in Growing Pigs

In both thermal conditions, greater postprandial concentrations of insulin and glucose were observed in response to the LPS-challenge with a longer-lasting hyperglycemia in pigs kept at 30 that at 24 °C. Overall, the hyperglycemic and hyperinsulinemic states result from a decreased responsiveness of skeletal muscle and adipose tissue glucose-transporters to insulin which leads to a decrease in glucose uptake (Sugita et al., 2002; Collier et al., 2008). As a consequence, a greater amount of glucose would be potentially available for cells involved in the immune response during inflammation (Spolarics and Spitzer, 1995; Spurlock, 1997). Because a greater glycemia was observed in pigs kept at high than at thermoneutral conditions, it might be a potential mechanism modulating pig capacity to overcome an inflammatory challenge. Furthermore, greater hepatic glucose production through gluconeogenesis and glycogenolysis is usually observed in response to immune challenges contributing to hyperglycemia (Webel et al., 1997). Accordingly, greater fasted glucose–circulating levels were recently reported in growing pigs in inflammatory state compared with healthy pigs (Chatelet et al., 2018). The LPS-induced persistent decrease in postprandial concentrations of NEFA in both thermal conditions observed in our study was a quite unexpected response since LPS-challenged pigs are usually in anorexic state and presumably would have to rely on body reserves mobilization to meet their nutritional needs. However, in the aforementioned study of Chatelet et al. (2018), lower fasted NEFA circulating levels were similarly observed in immune-challenged pigs. Nevertheless, a better characterization of plasma NEFA concentrations in response to inflammatory challenges is still needed.

The LPS-challenge resulted in decreased postprandial concentrations of α-amino nitrogen and urea with a more persistent urea response in pigs kept at 24 °C than at 30 °C. Lower postprandial concentions of urea were similarly reported in 20 kg BW pigs co-inoculated with Mycoplasma hyopneumoniae and H1N1 virus (Le Floc’h et al., 2014), and a 141% increase in the rate of protein synthesis was reported in chickens intraperitoneally administered a single dose of LPS (1 mg/kg BW) when compared with those receiving a control saline solution (Barnes et al., 2002). These results suggest that during an inflammatory or immune challenge, there is an increased demand for specific amino acids that are taken up by the liver and redirected to support the immune response preserving then their catabolism. Accordingly, in both thermal conditions, pigs had a persistent decrease in postprandial concentrations of Ala, Gly, His, Ile, Leu, Pro, Ser, Thr, Trp, and Val, suggesting a greater demand of these amino acids in such conditions. When exposed to sanitary or inflammatory challenges, pigs reduce their voluntary feed intake (Pastorelli et al., 2012) with a concomitant increase on their metabolism to support the synthesis of immune system compounds and other immune actions such as the fever response (Williams et al., 1997b; Campos et al., 2014b). For instance, our results suggest greater metabolic demand for branched-chain amino acids (BCAA) Ile, Leu, and Val in response to LPS which may be associated with their increased transamination and oxidation to be used as energy source for the immune function (Bruins et al., 2003). As reported previously (Campos et al., 2014b), this LPS model induces the synthesis acute phase proteins, such as haptoglobin, which have a high content in Thr and Trp (Reeds et al.,1994). Besides, Thr is one of the most abundant amino acids in immunoglobulins, and in mucins which are glycoproteins secreted in the intestinal lumen to protect the epithelium against injury (Le Floc’h et al., 2018). Accordingly, increased metabolic demand for Thr to support the synthesis of immunoglobulins, acute phase proteins, and mucins was reported in 10-kg BW pigs challenged with porcine reproductive and respiratory syndrome (McGilvray et al., 2019a). Concerning Trp, its catabolism is increased during inflammation through the indoleamine 2,3 dioxigenase (IDO) pathway. For instance, Le Floc’h et al. (2008) reported increased IDO activity in the lungs and associated lymph nodes in pigs suffering from chronic lung inflammation, and Melchior et al. (2004) observed a permanent 10-d decrease in circulating levels of Trp in 15- to 20-kg BW pigs challenged with complete Freund’s adjuvant. Our results also demonstrated a LPS-induced decrease in His circulating levels. In agreement, lower His levels were reported in young pigs challenged with LPS (Yoo et al., 1997) and in pigs coinfected with Mycoplasma hyopneumoniae and avian-like swine H1N1 virus strain (Le Floc’h et al., 2014).

The LPS also induced a decrease in Gln and Tyr, and an increase in Glu postprandial concentrations in both thermal conditions. However, although these responses were observed during the short- and medium-term phases of the LPS challenge in pigs kept at 24 °C, it was observed only during the short-term phase in pigs at 30 °C. As aforementioned, Gln is a major substrate for energy supply, gluconeogenesis, as well as precursor of other amino acids and glutathione. The lower postprandial levels of Gln are presumably then associated with a greater metabolic demand to support the inflammatory response and to restore whole-body homeostasis. In regard to Tyr, it is involved in the synthesis of acute phase proteins that in turn are particularly involved in a variety of defense-related responses. The longer-lasting decrease in urea postprandial concentrations and the greater demand for Gln and Tyr in pigs kept at 24 °C than at 30 °C suggests a greater demand for amino acids in pigs kept at thermoneutral conditions to support an increased LPS-induced inflammatory response and metabolic disturbance. Accordingly, although Phe postprandial concentration was decreased during the LPS-challenge in pigs kept at 24 °C, no differences were reported in pigs kept at 30 °C; this amino acid being of utmost importance in such conditions. Phenylalanine is an essential cofactor for NO synthesis by leucocytes and also upregulates macrophages activity (Li et al., 2007). The greater LPS-induced amino acid metabolic disturbance in pigs kept at thermoneutral than at high ambient temperature conditions is supported by our previous study (Campos et al., 2014b) demonstrating that LPS caused greater feed intake and growth depression in association with increased pro-inflammatory cytokines, haptoglobin, and cortisol circulating levels in pigs kept at thermoneutral conditions than in those previously acclimated to high ambient temperature.

Our results show an increased postprandial concentrations of Lys during the late phase of the LPS challenge evidencing its lower metabolic demand during a inflammatory cronic state. These findings are in close agreement with our previous study demonstrating a reduction in protein and fat deposition (−60 and −58 g/d on average, respectively) in LPS-challenged pigs, and in agreement with those of Williams et al. (1997a) reporting decreased Lys needs in association with lower body weight gain and nitrogen retention in piglets with high level of immune system activation when compared with their control counterparts. Accordingly, McGilvray et al. (2019b) reported a tendency for decreased Lys flux and then decreased Lys metabolic demand in 10-kg BW pigs challenged with repeated administration of LPS.

In conclusion, our study shows that an inflammatory challenge induced by repeated LPS injections induced important changes in insulin and nutrients postprandial metabolism. Particularly, increased circulating levels of glucose and insulin were observed in response to the LPS challenge and the magnitude of this response was greater in pigs kept at high than at thermoneutral conditions. This metabolic status contributes to increase the amount of glucose available to support the immune and nervous systems and then could be a potential mechanism modulating pig capacity to overcome an inflammatory challenge. In addition, irrespective of ambient temperature, LPS caused important changes in BCAA, His, Thr, and Trp profiles which might be associated with the role these AA in supporting the inflammatory response. Finally, our results suggest that LPS-induced effects on postprandial profiles of specific AA (Arg, Gln, Phe, and Tyr) may be modulated by ambient temperature.

Footnotes

1

We acknowledge Régis Janvier, Vincent Pievache, Francis Le Gouévec, Alain Chauvin, Julien Georges, and Mickaël Genissel for animal care, and Damián Escribano, Agnès Starck, Yolande Jaguelin, Françoise Thomas, Nadine Mézière, Michel Lefèbvre, Frédérique Mayeur, Raphaël Comte, and Sandrine Jaguelin for blood samplings and laboratory analysis. Financial support from the PhASE (Physiologie Animale et Systèmes d’Elevage) department of INRA and CAPES-Brazil (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) is gratefully acknowledged.

LITERATURE CITED

  1. Barnes D. M., Song Z., Klasing K. C., and Bottje W.. 2002. Protein metabolism during an acute phase response in chickens. Amino Acids. 22:15–26. [DOI] [PubMed] [Google Scholar]
  2. Bruins M. J., Deutz N. E., and Soeters P. B.. 2003. Aspects of organ protein, amino acid and glucose metabolism in a porcine model of hypermetabolic sepsis. Clin. Sci. (Lond). 104:127–141. doi: 10.1042/CS20020275 [DOI] [PubMed] [Google Scholar]
  3. Campos P. H. R. F., Labussière E., Hernández-García J., Dubois S., Renaudeau D., and Noblet J.. 2014a. Effects of ambient temperature on energy and nitrogen utilization in lipopolysaccharide-challenged growing pigs. J. Anim. Sci. 92:4909–4920. doi: 10.2527/jas.2014-8108 [DOI] [PubMed] [Google Scholar]
  4. Campos P. H. R. F., Le Floc’h N., Noblet J., and Renaudeau D.. 2017. Physiological responses of growing pigs to high ambient temperature and/or inflammatory challenges. R. Bras. Zootec. 46:537–544. doi: 10.1590/s1806-92902017000600009 [DOI] [Google Scholar]
  5. Campos P. H., Merlot E., Damon M., Noblet J., and Le Floc’h N.. 2014b. High ambient temperature alleviates the inflammatory response and growth depression in pigs challenged with escherichia coli lipopolysaccharide. Vet. J. 200:404–409. doi: 10.1016/j.tvjl.2014.04.001 [DOI] [PubMed] [Google Scholar]
  6. Campos P. H., Noblet J., Jaguelin-Peyraud Y., Gilbert H., Mormède P., Donzele R. F., Donzele J. L., and Renaudeau D.. 2014c. Thermoregulatory responses during thermal acclimation in pigs divergently selected for residual feed intake. Int. J. Biometeorol. 58:1545–1557. doi: 10.1007/s00484-013-0759-3 [DOI] [PubMed] [Google Scholar]
  7. Chacornac J. P., Barnouin J., and Houlier M. L.. 1993. [Automated micro-determination by transfer analyzer of circulating alpha-amino nitrogen]. Reprod. Nutr. Dev. 33:99–108. [PubMed] [Google Scholar]
  8. Chatelet A., Gondret F., Merlot E., Gilbert H., Friggens N. C., and Le Floc’h N.. 2018. Impact of hygiene of housing conditions on performance and health of two pig genetic lines divergent for residual feed intake. Animal 12:350–358. doi: 10.1017/S1751731117001379 [DOI] [PubMed] [Google Scholar]
  9. Chen Y., Li D., Dai Z., Piao X., Wu Z., Wang B., Zhu Y., and Zeng Z.. 2014. L-Methionine supplementation maintains the integrity and barrier function of the small-intestinal mucosa in post-weaning piglets. Amino Acids 46:1131–1142. doi: 10.1007/s00726-014-1675-5 [DOI] [PubMed] [Google Scholar]
  10. Collier R. J., Limesand S. W., Rhoads M. L., Rhoads R. P., and Baumgard L. H.. 2008. Homeorhesis during heat stress. In: Rauw W. M., editor, Resource allocation theory applied to farm animal production. Cabi, Wallingford, United Kingdom: p. 72–88. [Google Scholar]
  11. Heidemann S. M., and Glibetic M.. 2005. Heat stress protects against lung injury in the neutropenic, endotoxemic rat. Inflammation. 29:47–53. doi: 10.1007/s10753-006-8969-4 [DOI] [PubMed] [Google Scholar]
  12. Kimaro E. G., and Chibinga O. C.. 2013. Potential impact of climate change on livestock production and health in East Africa: a review. Lives. Res. Rural Dev. 25, Article 116. [Google Scholar]
  13. Le Floc’h N., Deblanc C., Cariolet R., Gautier-Bouchardon A. V., Merlot E., and Simon G.. 2014. Effect of feed restriction on performance and postprandial nutrient metabolism in pigs co-infected with mycoplasma hyopneumoniae and swine influenza virus. Plos One 9:e104605. doi: 10.1371/journal.pone.0104605 [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Le Floc’h N., Melchior D., and Sève B.. 2008. Dietary tryptophan helps to preserve tryptophan homeostasis in pigs suffering from lung inflammation. J. Anim. Sci. 86:3473–3479. doi: 10.2527/jas.2008-0999 [DOI] [PubMed] [Google Scholar]
  15. Le Floc’h N., Simongiovanni A., Corrent E., and Matte J. J.. 2017. Comparison of plasma tryptophan-related metabolites in crossbred Piétrain and Duroc pigs. J. Anim. Sci. 95:1606–1613. doi: 10.2527/jas.2016.1179 [DOI] [PubMed] [Google Scholar]
  16. Le Floc’h N., Wessels A., Corrent E., Wu G., and Bosi P.. 2018. The relevance of functional amino acids to support the health of growing pigs. Anim. Feed. Sci. Technol. 245:104–116. doi: 10.1016/j.anifeedsci.2018.09.007 [DOI] [Google Scholar]
  17. Li G., Ali I. S., and Currie R. W.. 2006. Insulin induces myocardial protection and HSP70 localization to plasma membranes in rat hearts. Am. J. Physiol. Heart Circ. Physiol. 291:H1709–H1721. doi: 10.1152/ajpheart.00201.2006 [DOI] [PubMed] [Google Scholar]
  18. Li P., Yin Y. L., Li D., Kim S. W., and Wu G.. 2007. Amino acids and immune function. Br. J. Nutr. 98:237–252. doi: 10.1017/S000711450769936X [DOI] [PubMed] [Google Scholar]
  19. Liu Y., Wang X., Hou Y., Yin Y., Qiu Y., Wu G., and Hu C. A.. 2017. Roles of amino acids in preventing and treating intestinal diseases: recent studies with pig models. Amino Acids 49:1277–1291. doi: 10.1007/s00726-017-2450-1 [DOI] [PubMed] [Google Scholar]
  20. McGilvray W. D., Klein D., Wooten H., Dawson J. A., Hewitt D., Rakhshandeh A. R., De Lange C. F. M., and Rakhshandeh A.. 2019a. Immune system stimulation induced by porcine reproductive and respiratory syndrome virus alters plasma free amino acid flux and dietary nitrogen utilization in starter pigs1. J. Anim. Sci. 97:2479–2492. doi: 10.1093/jas/skz120 [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. McGilvray W. D., Klein D., Wooten H., Dawson J. A., Hewitt D., Rakhshandeh A. R., de Lange C. F. M., and Rakhshandeh A.. 2019b. Immune system stimulation induced by Escherichia coli lipopolysaccharide alters plasma free amino acid flux and dietary nitrogen utilization in growing pigs. J. Anim. Sci. 97:315–326. doi: 10.1093/jas/sky401 [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Melchior D., Sève B., and Le Floc’h N.. 2004. Chronic lung inflammation affects plasma amino acid concentrations in pigs. J. Anim. Sci. 82:1091–1099. doi: 10.2527/2004.8241091x [DOI] [PubMed] [Google Scholar]
  23. Morales A., Cota S. E. M., Ibarra N. O., Arce N., Htoo J. K., and Cervantes M.. 2016. Effect of heat stress on the serum concentrations of free amino acids and some of their metabolites in growing pigs. J. Anim. Sci. 94:2835–2842. doi: 10.2527/jas2015-0073 [DOI] [PubMed] [Google Scholar]
  24. Morales A., Grageola F., García H., Arce N., Araiza B., Yáñez J., and Cervantes M.. 2014. Performance, serum amino acid concentrations and expression of selected genes in pair-fed growing pigs exposed to high ambient temperatures. J. Anim. Physiol. Anim. Nutr. (Berl). 98:928–935. doi: 10.1111/jpn.12161 [DOI] [PubMed] [Google Scholar]
  25. Pastorelli H., van Milgen J., Lovatto P., and Montagne L.. 2012. Meta-analysis of feed intake and growth responses of growing pigs after a sanitary challenge. Animal. 6:952–961. doi: 10.1017/S175173111100228X [DOI] [PubMed] [Google Scholar]
  26. Pearce S. C., Gabler N. K., Ross J. W., Escobar J., Patience J. F., Rhoads R. P. and Baumgard L. H.. 2013a. The effects of heat stress and plane of nutrition on metabolism in growing pigs. J. Anim. Sci. 91:2108–2118. doi: 10.2527/jas.2012-5738 [DOI] [PubMed] [Google Scholar]
  27. Pearce S. C., Mani V., Boddicker R. L., Johnson J. S., Weber T. E., Ross J. W., Rhoads R. P., Baumgard L. H., and Gabler N. K.. 2013b. Heat stress reduces intestinal barrier integrity and favors intestinal glucose transport in growing pigs. Plos One. 8:e70215. doi: 10.1371/journal.pone.0070215 [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pearce S. C., Mani V., Weber T. E., Rhoads R. P., Patience J. F., Baumgard L. H., and Gabler N. K.. 2013c. Heat stress and reduced plane of nutrition decreases intestinal integrity and function in pigs. J. Anim. Sci. 91:5183–5193. doi: 10.2527/jas.2013-6759 [DOI] [PubMed] [Google Scholar]
  29. Rakhshandeh A., and de Lange C. F.. 2012. Evaluation of chronic immune system stimulation models in growing pigs. Animal 6:305–310. doi: 10.1017/S1751731111001522 [DOI] [PubMed] [Google Scholar]
  30. Reeds P. J., Fjeld C. R., and Jahoor F.. 1994. Do the differences between the amino acid compositions of acute-phase and muscle proteins have a bearing on nitrogen loss in traumatic states? J. Nutr. 124:906–910. doi: 10.1093/jn/124.6.906 [DOI] [PubMed] [Google Scholar]
  31. Renaudeau D., Gourdine J. L., and St-Pierre N. R.. 2011. A meta-analysis of the effects of high ambient temperature on growth performance of growing-finishing pigs. J. Anim. Sci. 89:2220–2230. doi: 10.2527/jas.2010-3329 [DOI] [PubMed] [Google Scholar]
  32. Renaudeau D., Huc E., and Noblet J.. 2007. Acclimation to high ambient temperature in large white and caribbean creole growing pigs. J. Anim. Sci. 85:779–790. doi: 10.2527/jas.2006-430 [DOI] [PubMed] [Google Scholar]
  33. Rhoads R. P., Baumgard L. H., and Suagee J. K.. 2013. 2011 and 2012 early careers achievement awards: metabolic priorities during heat stress with an emphasis on skeletal muscle. J. Anim. Sci. 91:2492–2503. doi: 10.2527/jas.2012-6120 [DOI] [PubMed] [Google Scholar]
  34. Sanz Fernandez M. V., Johnson J. S., Abuajamieh M., Stoakes S. K., Seibert J. T., Cox L., Kahl S., Elsasser T. H., Ross J. W., Isom S. C., Rhoads R. P., and Baumgard L. H.. 2015a. Effects of heat stress on carbohydrate and lipid metabolism in growing pigs. Physiol. Rep. 3:e12315. doi: 10.14814/phy2.12315 [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Sanz Fernandez M. V., Stoakes S. K., Abuajamieh M., Seibert J. T., Johnson J. S., Horst E. A., Rhoads R. P., and Baumgard L. H.. 2015b. Heat stress increases insulin sensitivity in pigs. Physiol. Rep. 3:e12478. doi: 10.14814/phy2.12478 [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Sauvant D., Perez J. M., and Tran G.. 2002. Tables de composition et de valeur nutritive des matières premières destinées aux animaux d’élevage. INRA, Versailles. [Google Scholar]
  37. Shen Y. B., Weaver A. C., and Kim S. W.. 2014. Effect of feed grade L-methionine on growth performance and gut health in nursery pigs compared with conventional DL-methionine. J. Anim. Sci. 92:5530–5539. doi: 10.2527/jas.2014-7830 [DOI] [PubMed] [Google Scholar]
  38. Spolarics Z., and Spitzer J. J.. 1995. Acute endotoxin tolerance is accompanied by stimulated glucose use in macrophage rich tissues. Biochem. Biophys. Res. Commun. 211:340–346. doi: 10.1006/bbrc.1995.1816 [DOI] [PubMed] [Google Scholar]
  39. Spurlock M. E. 1997. Regulation of metabolism and growth during immune challenge: an overview of cytokine function. J. Anim. Sci. 75:1773–1783. doi: 10.2527/1997.7571773x [DOI] [PubMed] [Google Scholar]
  40. Sugita H., Kaneki M., Tokunaga E., Sugita M., Koike C., Yasuhara S., Tompkins R. G., and Martyn J. A.. 2002. Inducible nitric oxide synthase plays a role in LPS-induced hyperglycemia and insulin resistance. Am. J. Physiol. Endocrinol. Metab. 282:E386–E394. doi: 10.1152/ajpendo.00087.2001 [DOI] [PubMed] [Google Scholar]
  41. Wang C., Delcros J. G., Cannon L., Konate F., Carias H., Biggerstaff J., Gardner R. A., and Phanstiel IV O. 4th. 2003. Defining the molecular requirements for the selective delivery of polyamine conjugates into cells containing active polyamine transporters. J. Med. Chem. 46:5129–5138. doi: 10.1021/jm030223a [DOI] [PubMed] [Google Scholar]
  42. Watford M. 2008. Glutamine metabolism and function in relation to proline synthesis and the safety of glutamine and proline supplementation. J. Nutr. 138:2003S–2007S. doi: 10.1093/jn/138.10.2003S [DOI] [PubMed] [Google Scholar]
  43. Webel D. M., Finck B. N., Baker D. H., and Johnson R. W.. 1997. Time course of increased plasma cytokines, cortisol, and urea nitrogen in pigs following intraperitoneal injection of lipopolysaccharide. J. Anim. Sci. 75:1514–1520. doi: 10.2527/1997.7561514x [DOI] [PubMed] [Google Scholar]
  44. Williams N. H., Stahly T. S., and Zimmerman D. R.. 1997a. Effect of chronic immune system activation on body nitrogen retention, partial efficiency of lysine utilization, and lysine needs of pigs. J. Anim. Sci. 75:2472–2480. doi: 10.2527/1997.7592472x [DOI] [PubMed] [Google Scholar]
  45. Williams N. H., Stahly T. S., and Zimmerman D. R.. 1997b. Effect of level of chronic immune system activation on the growth and dietary lysine needs of pigs fed from 6 to 112 kg. J. Anim. Sci. 75:2481–2496. doi: 10.2527/1997.7592481x [DOI] [PubMed] [Google Scholar]
  46. Wu G., Bazer F. W., Satterfield M. C., Li X., Wang X., Johnson G. A., Burghardt R. C., Dai Z., Wang J., and Wu Z.. 2013. Impacts of arginine nutrition on embryonic and fetal development in mammals. Amino Acids 45:241–256. doi: 10.1007/s00726-013-1515-z [DOI] [PubMed] [Google Scholar]
  47. Wu X., Zhang Y., Liu Z., Li T. J., and Yin Y. L.. 2012. Effects of oral supplementation with glutamate or combination of glutamate and N-carbamylglutamate on intestinal mucosa morphology and epithelium cell proliferation in weanling piglets. J. Anim. Sci. 90(Suppl 4):337–339. doi: 10.2527/jas.53752 [DOI] [PubMed] [Google Scholar]
  48. Yoo S. S., Field C. J., and McBurney M. I.. 1997. Glutamine supplementation maintains intramuscular glutamine concentrations and normalizes lymphocyte function in infected early weaned pigs. J. Nutr. 127:2253–2259. doi: 10.1093/jn/127.11.2253 [DOI] [PubMed] [Google Scholar]
  49. Yu J., Yin P., Liu F., Cheng G., Guo K., Lu A., Zhu X., Luan W., and Xu J.. 2010. Effect of heat stress on the porcine small intestine: a morphological and gene expression study. Comp. Biochem. Physiol. A. Mol. Integr. Physiol. 156:119–128. doi: 10.1016/j.cbpa.2010.01.008 [DOI] [PubMed] [Google Scholar]

Articles from Journal of Animal Science are provided here courtesy of Oxford University Press

RESOURCES