@article{jacobi_moeser_corl_harrell_blikslager_odle_2012, title={Dietary Long-Chain PUFA Enhance Acute Repair of Ischemia-Injured Intestine of Suckling Pigs}, volume={142}, ISSN={0022-3166 1541-6100}, url={http://dx.doi.org/10.3945/jn.111.150995}, DOI={10.3945/jn.111.150995}, abstractNote={Abstract Infant formula companies have been fortifying formulas with long-chain PUFA for 10 y. Long-chain PUFA are precursors of prostanoids, which stimulate recovery of intestinal barrier function. Supplementation of milk with PUFA increases the content of arachidonic acid (ARA) in enterocyte membranes; however, the effect of this enrichment on intestinal repair is not known. The objective of these experiments was to investigate the effect of supplemental ARA on intestinal barrier repair in ischemia-injured porcine ileum. One-day-old pigs (n = 24) were fed a milk-based formula for 10 d. Diets contained no PUFA (0% ARA), 0.5% ARA, 5% ARA, or 5% EPA of total fatty acids. Following dietary enrichment, ilea were subjected to in vivo ischemic injury by clamping the local mesenteric blood supply for 45 min. Following the ischemic period, control (nonischemic) and ischemic loops were mounted on Ussing chambers. Transepithelial electrical resistance (TER) was measured over a 240-min recovery period. Ischemia-injured ileum from piglets fed 5% ARA (61.0 ± 14%) exhibited enhanced recovery compared with 0% ARA (16 ± 14) and 0.5% ARA (22.1 ± 14)-fed pigs. Additionally, ischemia-injured ileum from 5% EPA (51.3 ± 14)-fed pigs had enhanced recovery compared with 0% ARA-fed pigs (P < 0.05). The enhanced TER recovery response observed with ischemia-injured 5% ARA supplementation was supported by a significant reduction in mucosal-to-serosal flux of3H-mannitol and14C-inulin compared with all other ischemia-injured dietary groups (P < 0.05). A histological evaluation of ischemic ilea from piglets fed the 5% ARA showed reduced histological lesions after ischemia compared with the other dietary groups (P < 0.05). These data demonstrate that feeding elevated levels of long-chain PUFA enhances acute recovery of ischemia-injured porcine ileum.}, number={7}, journal={The Journal of Nutrition}, publisher={Oxford University Press (OUP)}, author={Jacobi, Sheila K. and Moeser, Adam J. and Corl, Benjamin A. and Harrell, Robert J. and Blikslager, Anthony T. and Odle, Jack}, year={2012}, month={May}, pages={1266–1271} }
 @article{jacobi_lin_corl_hess_harrell_odle_2011, title={Dietary Arachidonate Differentially Alters Desaturase-Elongase Pathway Flux and Gene Expression in Liver and Intestine of Suckling Pigs}, volume={141}, ISSN={0022-3166 1541-6100}, url={http://dx.doi.org/10.3945/jn.110.127118}, DOI={10.3945/jn.110.127118}, abstractNote={Because dietary arachidonate (ARA) and its eicosanoid derivatives are major regulators of intestinal homeostasis and repair following injury, we evaluated the effects of dietary ARA on desaturation and elongation of (13)C-18:2(n-6) and mRNA abundance of Δ-6-desaturase (FADS2), elongase (ELOVL5), and Δ-5-desaturase (FADS1) in liver and intestine. Day-old pigs (n = 96) were fed milk-based formula containing 0, 0.5, 2.5, or 5% ARA or 5% eicosapentaenoic acid of total fatty acids for 4, 8, and 16 d. In liver, the desaturation rate [nmol/(g tissue⋅h)] of (13)C-18:2(n-6) to (13)C-18:3(n-6) decreased 56% between 4 and 16 d but was not affected by diet. Whereas accumulation in (13)C-20:3(n-6) also decreased with age by 67%, it increased linearly with increasing dietary ARA (P < 0.06). In comparison, intestinal flux was ~50% less than liver flux and was unaffected by age, but desaturation to (13)C-18:3(n-6) increased linearly (by 57%) in pigs fed ARA diets (P < 0.001), equaling the rate observed in sow-fed controls. In both liver and intestine, alternate elongation to (13)C-20:2(n-6) (via Δ-8-desaturase) was markedly elevated in pigs fed the 0% ARA diet compared with all other dietary treatments (P < 0.01). Transcript abundance of FADS2, ELOVL5, and FADS1 was not affected in liver by diet (P > 0.05) but decreased precipitously between birth and d 4 (~70%; P < 0.05). In contrast, intestinal abundance of FADS2 and FADS1 increased 60% from d 4 to 16. In conclusion, dietary ARA regulated the desaturase-elongase pathway in a tissue-specific manner. In liver, ARA had modest effects on (n-6) fatty acid flux, and intestinal FADS2 activity and mRNA increased. Additionally, hepatic flux decreased with postnatal age, whereas intestinal flux did not change.}, number={4}, journal={The Journal of Nutrition}, publisher={Oxford University Press (OUP)}, author={Jacobi, Sheila K. and Lin, Xi and Corl, Benjamin A. and Hess, Holly A. and Harrell, Robert J. and Odle, Jack}, year={2011}, month={Feb}, pages={548–553} }
 @article{lin_bo_oliver_corl_jacobi_oliver_harrell_odle_2011, title={Dietary conjugated linoleic acid alters long chain polyunsaturated fatty acid metabolism in brain and liver of neonatal pigs}, volume={22}, ISSN={0955-2863}, url={http://dx.doi.org/10.1016/j.jnutbio.2010.09.002}, DOI={10.1016/j.jnutbio.2010.09.002}, abstractNote={Effects of dietary conjugated linoleic acid (CLA, 1% mixed isomers) on n-6 long-chain polyunsaturated fatty acid (LCPUFA) oxidation and biosynthesis were investigated in liver and brain tissues of neonatal piglets. Fatty acid β-oxidation was measured in tissue homogenates using [1-14C]linoleic acid (LA) and -arachidonic acid (ARA) substrates, while fatty acid desaturation and elongation were traced using [U-13C]LA and GC-MS. Dietary CLA had no effect on fatty acid β-oxidation, but significantly decreased n-6 LCPUFA biosynthesis by inhibition of LA elongation and desaturation. Differences were noted between our 13C tracer assessment of desaturation/elongation and simple precursor-product indices computed from fatty acid composition data, indicating that caution should be exercised when employing the later. The inhibitory effects of CLA on elongation/desaturation were more pronounced in pigs fed a low fat diet (3% fat) than a high fat diet (25% fat). Direct elongation of linoleic acid to C20:2n-6 via the alternate elongation pathway might play an important role in n-6 LCPUFA synthesis because more than 40% of the synthetic products of [U-13C]LA accumulated in [13C]20:2n-6. Overall, the data show that dietary CLA shifted the distribution of the synthetic products of [U-13C]LA between elongation and desaturation in liver and decreased the total synthetic products of [U-13C]LA in brain by inhibiting LA elongation to C20:2n-6. The impact of CLA on brain LCPUFA metabolism of the developing neonate merits consideration and further investigation.}, number={11}, journal={The Journal of Nutritional Biochemistry}, publisher={Elsevier BV}, author={Lin, Xi and Bo, Jenny and Oliver, Susan A. Mathews and Corl, Benjamin A. and Jacobi, Sheila K. and Oliver, William T. and Harrell, Robert J. and Odle, Jack}, year={2011}, month={Nov}, pages={1047–1054} }
 @article{corl_odle_niu_moeser_gatlin_phillips_blikslager_rhoads_2008, title={Arginine Activates Intestinal p70S6k and Protein Synthesis in Piglet Rotavirus Enteritis}, volume={138}, ISSN={0022-3166 1541-6100}, url={http://dx.doi.org/10.1093/jn/138.1.24}, DOI={10.1093/jn/138.1.24}, abstractNote={We previously showed that phosphorylation of p70 S6 kinase (p70(S6k)) in the intestine is increased during viral enteritis. In this study, we hypothesized that during rotavirus infection, oral Arg, which stimulates p70(S6k) activation, will further stimulate intestinal protein synthesis and mucosal recovery, whereas the p70(S6k) inhibitor rapamycin (Rapa) will inhibit mucosal recovery. Newborn piglets were fed a standard milk replacer diet supplemented with Arg (0.4 g x kg(-1) x d(-1), twice daily by gavage), Rapa (2 mg x m(-2) x d(-1)), Arg + Rapa, or saline (controls). They were infected on d 6 of life with porcine rotavirus. Three days postinoculation, we measured the piglets' body weight, fecal rotavirus excretion, villus-crypt morphology, epithelial electrical resistance in Ussing chambers, and p70(S6k) activation by Western blotting and immunohistochemistry. We previously showed a 2-fold increase in jejunal protein synthesis during rotavirus diarrhea. In this experiment, Arg stimulated jejunal protein synthesis 1.3-fold above standard medium, and the Arg stimulation was partially inhibited by Rapa. Small bowel stimulation of p70(S6k) phosphorylation and p70(S6k) levels were inhibited >80% by Rapa. Immunohistochemistry revealed a major increase of p70(S6k) and ribosomal protein S6 phosphorylation in the crypt and lower villus of the infected piglets. However, in Arg-treated piglets, p70(S6k) activation occurred over the entire villus. Jejunal villi of the Rapa-treated group showed inactivation of p70(S6k) and a decrease in mucosal resistance (reflecting increased permeability), the latter of which was reversed by Arg. We conclude that, early in rotavirus enteritis, Arg has no impact on diarrhea but augments intestinal protein synthesis in part by p70(S6k) stimulation, while improving intestinal permeability via a mammalian target of rapamycin/p70(S6k)-independent mechanism.}, number={1}, journal={The Journal of Nutrition}, publisher={Oxford University Press (OUP)}, author={Corl, Benjamin A. and Odle, Jack and Niu, Xiaomei and Moeser, Adam J. and Gatlin, Lori A. and Phillips, Oulayvanh T. and Blikslager, Anthony T. and Rhoads, J. Marc}, year={2008}, month={Jan}, pages={24–29} }
 @article{hess_corl_lin_jacobi_harrell_blikslager_odle_2008, title={Enrichment of Intestinal Mucosal Phospholipids with Arachidonic and Eicosapentaenoic Acids Fed to Suckling Piglets Is Dose and Time Dependent}, volume={138}, ISSN={0022-3166 1541-6100}, url={http://dx.doi.org/10.3945/jn.108.094136}, DOI={10.3945/jn.108.094136}, abstractNote={Infant formula companies began fortifying formulas with long-chain PUFA in 2002, including arachidonic acid (ARA) at approximately 0.5% of total fatty acids. The primary objective of this study was to determine the time-specific effects of feeding formula enriched with supra-physiologic ARA on fatty acid composition of intestinal mucosal phospholipids. One-day-old pigs (n = 96) were fed a milk-based formula for 4, 8, or 16 d. Diets contained either no PUFA (0% ARA, negative control), 0.5% ARA, 2.5% ARA, 5% ARA, or 5% eicosapentaenoic acid (EPA) of total fatty acids (wt:wt). Growth (299 +/- 21 g/d) and clinical hematology were unaffected by treatment (P > 0.6). Although minimal on d 4, concentrations of ARA in jejunal mucosa were enriched 47, 272 and 428% by d 8 and 144, 356, and 415% by d 16 in pigs fed the 0.5% ARA, 2.5% ARA, and 5% ARA diets, respectively, compared with the 0% ARA control pigs (P < 0.01). On d 16, ARA enrichment increased progressively with increasing dietary ARA supplementation from 0 to 2.5% but plateaued as dietary ARA rose to 5%. A similar pattern of ARA enrichment was observed in ileal mucosal phospholipids, but maximal enrichment in the ileum exceed that in the jejunum by >50%. As ARA increased, linoleic acid content decreased reciprocally. Although maximal enterocyte enrichment with EPA approached 20-fold by d 8, concentrations were only approximately 50% of those attained for ARA. Negligible effects on gross villus/crypt morphology were observed. These data demonstrate a dose-dependent response of intestinal mucosal phospholipid ARA concentration to dietary ARA with nearly full enrichment attained within 8 d of feeding formula containing ARA at 2.5% of total fatty acids and that supra-physiologic supplementation of ARA is not detrimental to growth.}, number={11}, journal={The Journal of Nutrition}, publisher={Oxford University Press (OUP)}, author={Hess, Holly A. and Corl, Benjamin A. and Lin, Xi and Jacobi, Sheila K. and Harrell, Robert J. and Blikslager, Anthony T. and Odle, Jack}, year={2008}, month={Nov}, pages={2164–2171} }
 @article{corl_harrell_moon_phillips_weaver_campbell_arthington_odle_2007, title={Effect of animal plasma proteins on intestinal damage and recovery of neonatal pigs infected with rotavirus}, volume={18}, ISSN={["1873-4847"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-36249015472&partnerID=MN8TOARS}, DOI={10.1016/j.jnutbio.2006.12.011}, abstractNote={Rotaviruses infect and elicit diarrhea in neonates of most mammalian species and cause 800,000 infant deaths a year. We used neonatal piglets to study the effects of dietary animal plasma proteins on intestinal health following rotavirus infection. Plasma protein contains a diverse mixture of functional components with biological activity and improves the health of animals challenged with other diarrhea-causing pathogens. In a 2×2 factorial design, we compared plasma protein- and soy protein-based diets in rotavirus-infected and noninfected piglets to determine if plasma protein reduced acute rotavirus intestinal damage or improved recovery. All infected animals shed rotavirus particles in their feces. Infected, plasma protein-fed piglets maintained growth rates similar to noninfected piglets in the first 3 days of infection; however, soy protein-fed piglets experienced reduced gains. Furthermore, infected, plasma protein-fed piglets showed no clinical signs of diarrhea. Infection reduced intestinal villus height and the villus height/crypt depth ratio by Day 3 of infection; however, reductions were not attenuated with dietary plasma protein. Infected, plasma protein-fed pigs maintained greater intestinal mucosa protein and estimated total lactase activity than infected, soy protein-fed piglets. Plasma proteins contain growth factors that may aid in rate of recovery as well as virus-binding proteins that may reduce infection pressure in the intestine. These data, combined with findings from other studies using plasma proteins in animal models of diarrhea, indicate the potential for using plasma proteins to improve the health of diarrheic neonates.}, number={12}, journal={JOURNAL OF NUTRITIONAL BIOCHEMISTRY}, author={Corl, Benjamin A. and Harrell, Robert J. and Moon, Hong Kil and Phillips, Oulayvahn and Weaver, Eric M. and Campbell, Joy M. and Arthington, John D. and Odle, Jack}, year={2007}, month={Dec}, pages={778–784} }