Medium chain fatty acids (MCFAs) are essential molecules for a wide range of pharmaceutical, biotechnological, and industrial applications. These are naturally occurring saturated or unsaturated fatty acids containing 6-12 carbons with complex and pH sensitive aggregation. Medium chain fatty acids such as capric acid (C10) or lauric acid (C12) have additionally been shown to exhibit antibacterial activity. A number of studies have observed the aggregation behavior of long chain fatty acid using the titration curves by molecular dynamic (MD) simulations.  In this study, we performed constant-pH coarse-grained MD simulations to determine pKa values and titration behavior using a two-states model for C10 and C12. In the simulations, pH was varied between 2 to 8 and pKa values were determined using the Hill equation. The pKa for C10 (capric acid) was found to be 4.8 and for C12 (lauric acid) 5.4, in good agreement with the literature values (4.9 and 5.3, respectively).

<p>Providing wholesome pork products to consumers involves raising healthy pigs to grow well and be feed efficient from birth to market. Raising these pigs starts with ensuring the sow is healthy and provided good nutrition in gestation and lactation. Therefore, this dissertation primarily focuses on research of gut modifying feed additives fed to sows in gestation and lactation (and to their progeny in Chapter 3) to enhance reproductive performance and litter growth to weaning (and in the nursery). In Chapter 2, a total of 606 sows and their progeny were used to determine if feeding gestating and lactating sows a proprietary strain of Pichia guilliermondi as a whole-cell inactivated yeast product (WCY; CitriStim, ADM Animal Nutrition, Quincy, IL) improves sow and litter performance in a commercial production system. Sows were fed a control (CON) diet or control diet fortified with 0.15% of the WCY from d 35 of gestation through lactation. Sows supplemented with WCY in gestation and lactation had a greater number of total born piglets by 0.45 pigs (P < 0.04), piglets born alive (P < 0.04), heavier born alive litter weights (P < 0.001), and greater post cross-foster litter size (P < 0.001) compared to CON fed sows. Litter size at weaning was increased by 0.54 pigs when sows were fed WCY compared to CON (P < 0.001). However, litter weaning weights and 21-day adjusted litter weaning weights were similar (P > 0.158) with the 21-day adjusted litter weaning weights being numerically greater for the WCY sows. The average piglet weaning weights from CON fed sows were heavier by 0.35 kg compared to WCY (P < 0.001). This increase in body weight of piglets from CON fed sows is partially explained by their 0.93 days longer lactation (P < 0.001) and may also be due to the smaller litter size nursed throughout lactation. The percent of litters treated for scours decreased from 38.3% to 14.2% when sows were fed WCY (P < 0.001). The distribution of birth and weaning weights was not different (P > 0.2461) between treatments.</p><p>Chapter 3 encompasses a sow experiment where progeny were followed onto the nursery for a 28-d study. Forty-seven sows and their progeny were used to determine if feeding gestating and lactating sows a Bacillus licheniformis direct-fed microbial (DFM), an organic acid blend of medium and short-chain fatty acids (OA), or in combination improves sow lactation feed and water intake, litter growth, and subsequent reproductive performance. At weaning, offspring were fed a positive control diet (PC), negative control diet (NC), or a diet representative of their dam’s treatment to determine if there is an additive benefit to also feeding DFM and/or OA to nursery pigs in addition to their dams. On approximately d 80 of gestation, sows were fed one of four diets in a 2  2 factorial design: 1) gestation control (CON), 2) CON with DFM (1.6x109 CFU/kg of complete feed), 3) CON with 0.4% OA, 4) CON with both DFM and OA. Dietary treatments were also fed throughout lactation. Sows fed the OA diets had fewer mummies per litter (P < 0.010) compared to diets not containing OA. Sows fed diets with the DFM gave birth to lighter pigs born alive (1.5 vs. 1.7 kg; P < 0.003) compared to non-DFM fed sows, and a tendency for an interaction (P < 0.092) existed where feeding DFM+OA lessened the decrease in born alive BW. There was a tendency (P < 0.093) for pigs from DFM fed sows to also be lighter at weaning (5.8 vs. 6.2 kg) compared to pigs from sows not fed DFM, with no differences in litter sizes at weaning (P < 0.815). There was a tendency (P < 0.079) for the DFM to decrease the amount of sow BW loss in lactation compared to sows not fed the DFM (approximately 6 vs. 8% BW loss, respectively). The maintained BW in lactation was likely related to DFM sows numerically (P < 0.124) consuming 8.4% more feed during d 7-14 of lactation and 6.4% more feed (P < 0.234) from d 1 of lactation to weaning. The interaction was approaching a trend (P < 0.133) where sows fed DFM returned to estrus 1.0 day sooner than CON, but only 0.4 days sooner when sows were fed the DFM+OA diet.</p><p>Progeny weaned from these sows (n = 384, Initial BW = 6.15 kg) were blocked by initial BW and sex and allotted (6 pigs/pen, 8 pens/treatment) to one of 8 nursery treatments. Pigs from CON sows were fed a negative (NC; no antibiotics, no pharmacological Zn or Cu) or positive (PC; neomycin-oxytetracycline in phases 1 and 2 (827 and 551 ppm) and carbadox in phases 3 and 4 (55 ppm)) control diet. Pigs from sows fed DFM, OA, or DFM+OA were fed the NC diet or a diet representative of their dam’s treatment. Diets with DFM contained 1.6x109 CFU/kg of complete feed and diets with OA contained 0.5, 0.4, 0.3, and 0.0% OA in phases 1-4, respectively. Weaning weight was used as a covariate for nursery performance due to the DFM offspring being significantly lighter at weaning. For all phases and overall, PC fed pigs had greater ADG (P < 0.003) and ADFI (P < 0.059) than NC pigs. PC fed pigs had greater G:F (P < 0.010) than NC pigs for all phases and overall except d 21-28 (P < 0.532). Feeding DFM or OA in sow diets improved (interaction; P < 0.049) nursery pig G:F, but DFM+OA offspring had similar G:F compared to NC pigs from CON fed sows for d 7-14, 0-14, 0-21, and 0-28. Feeding DFM or OA to sows and their progeny decreased ADFI (interaction; P < 0.042) but improved G:F (interaction; P < 0.028) for d 7-14 and 0-14 with DFM+OA having similar performance to NC. For d 14-21 and 0-21, feeding DFM or OA to sows and their progeny decreased ADFI whereas DFM+OA increased ADFI above NC (interaction; P < 0.019). Overall, d 0-28, feeding DFM or OA to sows and their progeny improved G:F (interaction; P < 0.001) with DFM+OA having poorer G:F compared to NC. When the DFM was fed to sows and nursery pigs, progeny harvested on d 6 post-weaning had a decreased ratio of villus height to crypt depth (P < 0.035) compared to sows and pigs not consuming the DFM (average 1.34 vs. 1.67). Comparing pigs fed PC vs. NC from CON fed sows, expression of interleukin 10 (IL-10) was greater (0.51-fold increase; P < 0.046) for NC pigs than PC pigs. Expression of occludin (OCLN) was lower (P < 0.010) when OA was fed to the sows and pigs compared to when OA was not fed to the sows and pigs (0.78 vs. 1.00, respectively).</p><p>Chapter 4 is the only chapter that does not include maternal nutrition. In this chapter, maternal line gilts (Topigs Norsvin TN70) were bred with frozen semen from Duroc boars born from 2000 to 2017 divided into two genetic groups: semen from boars born in 2000 to 2005 and 2011 to 2017. These genetic groups had vastly different terminal sire indexes (TSI) of 88.2 and 112.0 for 2000 to 2005 and 2011 to 2017, respectively. A total of 155 pigs were weaned into 44 pens in a wean-to-finish facility to determine if genetics from two decades of sires and sex of the progeny impact progeny growth performance and carcass characteristics. The expected large growth performance differences indicated by the TSI’s of the two genetic groups were not observed. However, barrows had greater feed intake (P < 0.031) and fatter carcasses (P < 0.004) than the more feed efficient (P < 0.006) and leaner (P < 0.015) gilts in this study. Modern swine genetics have been selected to be leaner and results from this study agree, although the differences in live scan and carcass measurements were not as large as expected. The lack of differences between genetic groups could possibly be due to environmental differences including nutrition and rearing conditions from when these sires were alive compared to what was experienced by these progeny.</p><p>In conclusion, feeding gestating and lactating sows a proprietary strain of Pichia guilliermondi as a whole-cell inactivated yeast product increased the number of piglets born and weaned as well as decreased the prevalence of scours during lactation. Feeding a Bacillus licheniformis DFM to sows may decrease pig born alive weight and subsequent weaning weight but reduce sow BW loss through 6.4% more lactation feed intake, quickening the return to estrus. Other than decreasing the number of mummies per litter, feeding the OA alone or in combination did not improve sow reproductive or litter growth performance in this study. Feeding DFM or OA to sows or their offspring may improve nursery feed efficiency but did not result in a difference in ADG or final BW in this study. Feeding the combination diet (DFM+OA) to the sow and nursery pigs tended to increase ADFI. Feeding antibiotics post-weaning continued to improve pig growth performance resulting in 2.7 kg heavier pigs at the end of the 28-d nursery period. Lastly, the expected large growth performance differences indicated by the TSI’s of two genetic groups created by using frozen semen from boars born in 2000 to 2005 and 2011 to 2017 were not observed.</p>

The overall purpose of this thesis is to understand the impact of management on commercial egg layers, whether that be environmental-related, health-related, or other possible stressors within the pullet and post-peak phases. Furthermore, the study seeks to examine what effects to performance and production these impacts may induce within a commercial layer in differing phases, specifically the pullet and post-peak phases. Chapter two explores into coccidiosis within the pullet phase, which induced by a commercial vaccine, can provide stress to a pullet, lowering protection against infection, and seriously compromising its growth and development into peak lay. Chapter three explores into the post-peak phase, a transition from a caged system of production to cage-free system of production was selected. incorporating multiple differing environmental stimuli that can induce stress. If commercial layers prove to possess the capabilities to adapt to these impacts in multiple phases, the possibility of extended production is possible.

Les acides gras saturés à chaîne moyenne (AGCM) ont été décrits comme potentiellement bénéfiques pour réguler la balance énergétique chez l’homme. Cependant, la récente découverte de l’activation de la ghréline, hormone gastrique orexigène, par l’acide octanoïque (C8:0), ajoute un nouveau niveau de complexité dans la compréhension des effets physiologiques des AGCM. En effet, pour être reconnue par son récepteur hypophysaire, la ghréline doit préalablement être octanoylée par la Ghréline O-Acyltransférase (GOAT). Or, les paramètres régulés par la ghréline ainsi modifiée s’opposent aux effets connus des AGCM, en favorisant la prise alimentaire et la prise de masse. L’élaboration d’inhibiteurs de la GOAT constitue donc une stratégie thérapeutique nouvelle pour lutter contre l’obésité. Les AGCM sont essentiellement apportés par l’alimentation,leur biosynthèse endogène n’ayant été décrite que dans les cellules de la glande mammaire en lactation. Etudier l’impact du C8:0 d’origine alimentaire sur l’octanoylation de la ghréline est donc d’autant plus pertinent, car celui-ci est suspecté de fournir à la GOAT le co-substrat nécessaire à l’octanoylation. Afin de mieux comprendre l’apparente contradiction entre les effets connus des AGCM sur la masse corporelle et la satiété, et l’effet de l’octanoylation de la ghréline, quatre approches ont été mises en œuvre: (1) Etude des effets physiologiques du C8:0 à différentes doses sur l’axe ghréline-GOAT et sur le métabolisme chez le rat adulte, (2) Etude de l’absorption gastrique du C8:0 par inhibition de la lipase préduodénale, chez le / Medium chain fatty acids (MCFA) have been described as potentially beneficial for regulating human energetic balance. However, the recent discovery of the orexigenic ghrelin activation by octanoic acid revealed a new level of complexity in MCFA effects. Ghrelin must be octanoylated by the Ghrelin O-Acyltransferase (GOAT) to bind its pituitary receptor. Interestingly, the effects mediated by the post-translationally modified ghrelin seem opposed to MCFA known effects, increasing food intake and body weight. Development of GOAT inhibitors could then constitute a therapeutic strategy against obesity. MCFA are mainly provided by the diet, as their endogenous synthesis has only been described in lactating mammary glands. Dietary caprylic acid is then suspected to provide the GOAT enzyme with octanoyl- CoA co-substrates necessaryfor the acyl modification of ghrelin. My objective is to understand the discrepancy between the formerly described beneficial effects of dietary MCFAs on body weight loss and the C8:0 newly reported effect on appetite stimulation via ghrelin octanoylation. This thesis is divided into four parts: (1) Study of C8:0 physiological effects on ghrelin-GOAT axis, in rat, (2) Study of C8:0 gastric absorption by inhibition of preduodenal lipase, in young rat, (3) Study of C8:0 metabolism in gastric cells in vitro, (4) Preliminary study of GOAT activity in vitro.