Chronic social stress in pigs impairs intestinal barrier and nutrient transporter function, and alters neuro-immune mediator and receptor expression.

Psychosocial stress is a major factor driving gastrointestinal (GI) pathophysiology and disease susceptibility in humans and animals. The mechanisms governing susceptibility to stress-induced GI disease remain poorly understood. In the present study, we investigated the influence of chronic social stress (CSS) in pigs, induced by 7 d of chronic mixing/crowding stress, on intestinal barrier and nutrient transport function, corticotropin releasing factor (CRF) signaling and immunological responses. Results from this study showed that CSS resulted in a significant impairment of ileal and colonic barrier function indicated by reduced transepithelial electrical resistance (TER) in the ileum and increased FD4 flux in the ileum (by 0.8 fold) and colon (by 0.7 fold). Ileal sodium glucose linked transporter 1 (SGLT-1) function, measured as glucose-induced changes in short-circuit current (Isc), was diminished (by 52%) in CSS pigs, associated with reduced body weight gain and feed efficiency. Although reductions in SGLT-1 function were observed in CSS pigs, mRNA expression for SGLT-1, villus heights were increased in CSS pigs. Corticotropin releasing factor (CRF) mRNA was upregulated (by 0.9 fold) in the ileum of CSS pigs but not in the colon. Urocortin 2 (Ucn2) mRNA was upregulated (by 1.5 fold) in the colon of CSS pigs, but not in the ileum. In CSS pigs, a downregulation of pro-inflammatory cytokines mRNA (IL1B, TNFA, IL8, and IL6) was observed in both ileum and colon, compared with controls. In contrast CSS induced a marked upregulation of mRNA for IL10 and mast cell chymase gene (CMA1) in the ileum and colon. Together, these data demonstrate that chronic stress in pigs results in significant alterations in intestinal barrier and nutrient transport function and neuro-immune mediator and receptor expression

Magnolol as a Protective Antioxidant Alleviates Rotenone-Induced Oxidative Stress and Liver Damage through MAPK/mTOR/Nrf2 in Broilers

This study aimed to investigate the protective effects and molecular mechanism of magnolol supplementation on rotenone-induced oxidative stress in broilers. Two hundred and eighty-eight old male AA broilers were randomly divided into four groups: the CON group: basic diet with sunflower oil injection; the ROT group: basic diet with 24 mg/kg BW rotenone; the MAG + ROT group: basic diet with 300 mg/kg magnolol and rotenone injection; and the MAG group: basic diet with 300 mg/kg magnolol and sunflower oil injection. At 21–27 days of age, the broilers in each group were intraperitoneally injected with rotenone (24 mg/kg BW) or the same volume of sunflower oil. The results showed that magnolol reversed the decrease in ADG post-injection and FBW via rotenone induction. Compared to the ROT group, MAG + ROT group enhanced the average daily gain post injection (p p p < 0.05). The hepatocyte apoptosis and the mRNA expression of apoptosis-related signaling pathway in the ROT group increased, but magnolol supplementation inhibited rotenone-induced apoptosis through the Nrf2 signaling pathway. Through RNA transcriptome analysis, there were 277 differential genes expressions (DEGs) among the CON group with ROT group, and 748 DEGs were found between the ROT group and the MAG + ROT group. KEGG pathway enrichment found that magnolol relieved rotenone-induced energy metabolism disorder and oxidative damage through signaling pathways such as MAPK and mTOR. In conclusion, magnolol attenuates rotenone-induced hepatic injury and oxidative stress of broilers, presumably by restoring hepatic antioxidant function via the MAPK/mTOR/Nrf2 signaling pathway

Evaluation of Nitrogen-Corrected Apparent Metabolizable Energy and Standardized Ileal Amino Acid Digestibility of Different Sources of Rice and Rice Milling Byproducts in Broilers

Rice, broken rice (BR), and full-fat rice bran (FFRB) from six different origins were analyzed for their chemical composition, nitrogen-corrected apparent metabolized energy (AMEn), and standardized amino acid digestibility (SIAAD) in 14-day-old and 28-day-old Arbor Acres broilers. Results showed broilers fed with rice and BR had a similar AMEn regardless of the rice and BR having different CP, EE, NDF, ADF, and ash content. FFRB containing significantly different CP, EE, NDF, ADFm and starch presented variable AMEn (p &lt; 0.05), suggesting that starch content in rice and its byproducts contributed most to the AMEn of broilers. The regression equation of AMEn = 14.312 − (0.198 × NDF) and AMEn = 6.491 + (0.103 × Starch) were feasible to integrally predict AMEn of broilers fed to rice and its byproducts. Moreover, 28-day-old broilers had higher SIAAD than 14-day-old ones. The SIAAD of rice were higher than BR and FFRB except for Met, Cys, Thr, and Tyr in 14-day-old broilers (p &lt; 0.05), and the SIAAD of His, Asp, and Ser in BR were higher than FFRB (p &lt; 0.05). In 28-day-old broilers, the SIAAD of Leu, Trp, Asp, Gly, and Pro of rice were still higher than BR and FFRB (p &lt; 0.05), but BR and FFRB had no significant differences (p &gt; 0.05). The regression equations to estimate the SIAAD of Thr, Lys, and Met were: Met = 81.46 + (0.578 × CP), Thr = 0.863 + (6.311 × CP), and Trp = 102.883 − (1.77 × CP), indicating that CP content in rice and its byproducts was likely a major factor for prediction of SIAAD

Protective Effects of L-Theanine on IPEC-J2 Cells Growth Inhibition Induced by Dextran Sulfate Sodium via p53 Signaling Pathway

L-theanine is a nonprotein amino acid found in tea leaves and has been widely used as a safe food additive in beverages or foods because of its varied bioactivities. The aim of this study was to reveal the in vitro gastrointestinal protective effects of L-theanine in DSS-induced intestinal porcine enterocyte (IPEC-J2) cell models using molecular and metabolic methods. Results showed that 2.5% dextran sulfate sodium (DSS) treatment inhibited the cell proliferation of IPEC-J2 and blocked the normal operation of the cell cycle, while L-theanine pretreatment significantly preserved these trends to exert protective effects. L-theanine pre-treatment also up-regulated the EGF, CDC2, FGF2, Rb genes and down-regulated p53, p21 proliferation-related mRNA expression in DSS-treated cells, in accompany with p53 signaling pathway inhibition. Meanwhile, metabolomics analysis revealed that L-theanine and DSS treated IPEC-J2 cells have different metabolomic profiles, with significant changes in the key metabolites involved in pyrimidine metabolism and amino acid metabolism, which play an important role in nucleotide metabolism. In summary, L-theanine has a beneficial protection in DSS-induced IPEC-J2 cells via promoting proliferation and regulating metabolism disorders

Honokiol Alleviates High-Fat Diet-Induced Obesity of Mice by Inhibiting Adipogenesis and Promoting White Adipose Tissue Browning

Honokiol (HON) is one of the main biological active components of the traditional Chinese medicine Magnolia officinalis and has many health benefits. The aim of this study was to investigate whether HON could alleviate obesity in mice by inhibiting adipogenesis and promoting the browning of white adipose tissue (WAT). C57BL/6 mice were divided into five groups and fed with a normal diet (ND), high-fat diet (HFD), or HFD supplemented with 200 (H200), 400 (H400), or 800 (H800) mg/kg BW HON for 8 weeks. The results showed that the mice fed HFD plus HON had lower body fat ratios (BFRs) and smaller adipocyte diameters in the epididymal WAT compared with those of the HFD group. With a proteomics analysis, the HON group upregulated 30 proteins and downregulated 98 proteins in the epididymal WAT of mice, and the steroid O-acyltransferase 1 (SOAT1) was screened as a key protein. The HON supplement prevented HFD-induced adipogenesis by reduced the mRNA and protein expression of SOAT1 and CCAAT/enhancer-binding protein-α (C/EBPα), suggesting that SOAT1 might play an important role in regulating adipogenesis. Moreover, HON treatment increased the expression of proteins related to the classical pathways of energy and lipid metabolism, such as AMP-activated kinase (AMPK) and acetyl-CoA carboxylase (ACC), and promoted the browning of epididymal WAT by upregulation of the protein expression of uncoupling protein 1 (UCP1) in the HFD mice. In conclusion, these results suggest that HON supplements could prevent increases in body fat for HFD mice by suppressing adipogenesis and promoting WAT browning

Effects of chronic social stress on ileal mucosal cytokine gene and protein expression.

<p>Relative mRNA expression of <b>(A)</b> <i>TNFA</i>, <b>(B)</b> <i>IL8</i>, <b>(C)</b> <i>IL1B</i>, <b>(D)</b> <i>IFNG</i>, <b>(E)</b> <i>IL6</i>, and <b>(F)</b> <i>IL10</i> in ileal mucosa from pigs subjected to 7 d chronic social stress. All values are relative to the expression levels measured in control pigs. Ileal mucosal concentrations of <b>(G)</b> IL-8, <b>(H)</b> TNFα and <b>(I)</b> IL1β from pigs subjected to 7 d chronic social stress. Values are means ± SE (n = 6 per treatment). ** indicates significant difference, P ≤ 0.01; * indicates significant difference P ≤ 0.05. Student’s T-test.</p

Effects of chronic social stress in pigs on intestinal glucose transporter activity and transporter expression.

<p><b>(A)</b> Glucose-induced Δ<i>I</i>_sc. Relative mRNA expression of <b>(B)</b> SGLT-1, <b>(C)</b> GLUT2, <b>(D)</b> GLUT5, <b>(E)</b> B0AT1, <b>(F)</b> ATB0⁺, and <b>(G)</b> EAAT3. All values are relative to the expression levels measured in control pigs. Values are means ± SE (n = 6 per treatment). ** indicates significant difference, P ≤ 0.01; * indicates significant difference, P ≤ 0.05; P = 0.07 by Student’s t-test.</p

Effects of chronic social stress in pigs on ileal and colonic TER, <i>I</i>_sc, and FD4 flux rates.

<p><b>(A)</b> Ileal TER. <b>(B)</b> Basal ileal <i>I</i>_sc. <b>(C)</b> Ileal FD4 flux rate. <b>(D)</b> Colonic TER. <b>(E)</b> Basal colonic <i>I</i>_sc. <b>(F)</b> Colonic FD4 flux rate. Values are means ± SE (n = 6 per treatment). ** indicates significant difference, P ≤ 0.01.</p

Effects of chronic social stress in pigs on mast cell chymase and tryptase mRNA expression and mast cell tryptase staining in ileum and colon.

<p>Relative mRNA expression of <b>(A)</b> ileal <i>CMA1</i> and <b>(B)</b> ileal <i>MCT7</i>. <b>(C)</b> Ileal submucosal mast cell tryptase-positive counts. Relative mRNA expression of <b>(D)</b> colonic <i>CMA1</i> and <b>(E)</b> colonic <i>MCT7</i>. <b>(F)</b> Colonic submucosal mast cell tryptase-positive counts. mRNA values are relative to the expression level measured in control pigs. Values are means ± SE (n = 6 per treatment). ** indicates significant difference, P ≤ 0.01; * indicates significant difference, P ≤ 0.05; P = 0.07 (C), P = 0.09 (F) by Students T-test.</p

Oral administration of dibutyryl adenosine cyclophosphate improved growth performance in weaning piglets by enhancing lipid fatty acids metabolism

Dibutyryl adenosine cyclophosphate (dbcAMP-Ca), an analog of cyclic adenosine monophosphate (cAMP), plays greater roles in regulating physiological activities and energy metabolism than cAMP. The aim of this study was to investigate the effect of oral administration of dbcAMP-Ca on growth performance and fatty acids metabolism in weaning piglets. A total of 14 early weaning piglets (7 ± 1 d of age, 3.31 ± 0.09 kg, Landrace × Large White × Duroc) were randomly divided into 2 groups: control group and dbcAMP-Ca group, and the piglets received 7 mL of 0.9% NaCl or 1.5 mg dbcAMP-Ca dissolved in 7 mL of 0.9% NaCl per day for 10 d, respectively. The results showed that the average daily gain (ADG) increased by 109.17% (P < 0.05) in the dbcAMP-Ca group compared with the control group. Besides, dbcAMP-Ca significantly decreased blood high density lipoprotein cholesterol (HDLC) concentration (P < 0.05) and significantly increased blood low density lipoprotein cholesterol (LDLC) concentration (P ＜ 0.05) compared with the control group. Further, liver C18:2n6t content significantly increased in dbcAMP-Ca group (P < 0.05) compared with the control group. With the increase of C18:2n6t content, the mRNA expression levels of peroxisome proliferator-activated receptor α (PPARα) and hormone sensitive glycerol three lipase (HSL), of which genes are related to lipid metabolism, were also significantly increased (P < 0.05 or P < 0.01). All of the results indicated that dbcAMP-Ca improved the ADG, which was probably done by regulating fatty acids metabolism in the liver of weaning piglets. Keywords: Dibutyryl adenosine cyclophosphate, Growth performance, Lipid metabolism, Peroxisome proliferator-activated receptor α, Hormone sensitive glycerol three lipase, Early weaning piglet