Feeding Parenteral Nutrition in the Neonatal Period Programs Dyslipidemia in Adulthood in Yucatan Miniature Pigs.

Background: Early nutritional challenges can lead to permanent metabolic changes, increasing risk of developing chronic diseases later in life. Total parenteral nutrition (TPN) is a life-saving nutrition regimen, used especially in intrauterine growth-restricted (IUGR) neonates. Early TPN feeding alters metabolism, but whether these alterations are permanent is unclear.

Dietary Methionine Enhances Portal Appearance of Guanidinoacetate and Synthesis of Creatine in Yucatan Miniature Piglets.

Background: Creatine plays a significant role in energy metabolism and positively impacts anaerobic energy capacity, muscle mass, and physical performance. Endogenous creatine synthesis requires guanidinoacetic acid (GAA) and methionine. GAA can be an alternative to creatine supplements and has been tested as a beneficial feed additive in the animal industry.

Lysine Dipeptide Enhances Gut Structure and Whole-Body Protein Synthesis in Neonatal Piglets with Intestinal Atrophy.

Background: Parenteral nutrition (PN) is often a necessity for preterm infants; however, prolonged PN leads to gut atrophy, weakened gut barrier function, and a higher risk of intestinal infections. Peptide transporter-1 (PepT1) is a di- or tripeptide transporter in the gut and, unlike other nutrient transporters, its activity is preserved with the onset of intestinal atrophy from PN. As such, enteral amino acids in the form of dipeptides may be more bioavailable than free amino acids when atrophy is present.

Neonatal Piglets Can Synthesize Adequate Creatine, but Only with Sufficient Dietary Arginine and Methionine, or with Guanidinoacetate and Excess Methionine.

Background: Suckling piglets synthesize most of their creatine requirement, which consumes substantial amounts of arginine in order to synthesize guanidinoacetic acid (GAA) and methionine in order to transmethylate GAA to creatine.

Objectives: To determine whether supplemental GAA or creatine spare arginine and/or methionine for protein synthesis and, if GAA is supplemented, whether excess methionine is needed for conversion to creatine.

Methods: Yucatan miniature piglets (9-11 days old; both sexes) were fed 1 of 5 elemental diets for 5 days: 1) low arginine (0.

Effects of supplemental creatine and guanidinoacetic acid on spatial memory and the brain of weaned Yucatan miniature pigs.

The emergence of creatine as a potential cognitive enhancement supplement for humans prompted an investigation as to whether supplemental creatine could enhance spatial memory in young swine. We assessed memory performance and brain concentrations of creatine and its precursor guanidinoacetic acid (GAA) in 14-16-week-old male Yucatan miniature pigs supplemented for 2 weeks with either 200 mg/kg∙d creatine (+Cr; n = 7) or equimolar GAA (157 mg/kg∙d) (+GAA; n = 8) compared to controls (n = 14). Spatial memory tests had pigs explore distinct sets of objects for 5 min.

The Kidneys Are Quantitatively More Important than Pancreas and Gut as a Source of Guanidinoacetic Acid for Hepatic Creatine Synthesis in Sow-Reared Yucatan Miniature Piglets.

Background: Arginine:glycine amidinotransferase, necessary for the conversion of arginine (Arg) to guanidinoacetic acid (GAA), is expressed mainly in kidney and pancreas. The methylation of GAA to creatine (Cre) primarily occurs in the liver. The role of the gut in Cre homeostasis has not been characterized.

Photoprotection But Not N-acetylcysteine Improves Intestinal Blood Flow and Oxidation Status in Parenterally Fed Piglets.

Objectives: The purpose of the present study was to determine if protecting parenteral nutrition solutions from ambient light and supplementing with N-acetylcysteine (NAC) improves mesenteric blood flow, gut morphology, and oxidative status of parenterally fed neonates.

Methods: Neonatal Yucatan miniature piglets (n = 23, 7-11 days old) were surgically fitted with central venous catheters and an ultrasonic blood flow probe around the superior mesenteric artery. Piglets were fed continuously for 7 days either light-protected (LP) or light-exposed (LE) complete parenteral nutrition that was enriched with either NAC or alanine (ALA).

Betaine or folate can equally furnish remethylation to methionine and increase transmethylation in methionine-restricted neonates.

Methionine partitioning between protein turnover and a considerable pool of transmethylation precursors is a critical process in the neonate. Transmethylation yields homocysteine, which is either oxidized to cysteine (i.e.

Aluminum Exposure from Parenteral Nutrition: Early Bile Canaliculus Changes of the Hepatocyte.

Neonates on long-term parenteral nutrition (PN) may develop parenteral nutrition-associated liver disease (PNALD). Aluminum (Al) is a known contaminant of infant PN, and we hypothesize that it substantially contributes to PNALD. In this study, we aim to assess the impact of Al on hepatocytes in a piglet model.

Creatine supplementation to total parenteral nutrition improves creatine status and supports greater liver and kidney protein synthesis in neonatal piglets.

BackgroundCreatine is not included in commercial pediatric parenteral products; the entire creatine requirement must be met by de novo synthesis from arginine during parenteral nutrition (PN). Poor arginine status is common during PN in neonates, which may compromise creatine accretion. We hypothesized that creatine supplementation will improve creatine status and spare arginine in PN-fed piglets.

Protein Synthesis in Mucin-Producing Tissues Is Conserved When Dietary Threonine Is Limiting in Piglets.

Background: The neonatal gastrointestinal tract extracts the majority of dietary threonine on the first pass to maintain synthesis of threonine-rich mucins in mucus. As dietary threonine becomes limiting, this extraction must limit protein synthesis in extraintestinal tissues at the expense of maintaining protein synthesis in mucin-producing tissues.

Objective: The objective was to determine the dietary threonine concentration at which protein synthesis is reduced in various tissues.

Dietary methyl donors affect in vivo methionine partitioning between transmethylation and protein synthesis in the neonatal piglet.

Methionine metabolism is critical during development with significant requirements for protein synthesis and transmethylation reactions. However, separate requirements of methionine for protein synthesis and transmethylation are difficult to define because after transmethylation, demethylated methionine is either irreversibly oxidized to cysteine during transsulfuration, or methionine is regenerated by the dietary methyl donors, choline (via betaine) or folate during remethylation. We hypothesized that remethylation contributes significantly to methionine availability and affects partitioning between protein and transmethylation.

Restriction of dietary methyl donors limits methionine availability and affects the partitioning of dietary methionine for creatine and phosphatidylcholine synthesis in the neonatal piglet.

Methionine is required for protein synthesis and provides a methyl group for >50 critical transmethylation reactions including creatine and phosphatidylcholine synthesis as well as DNA and protein methylation. However, the availability of methionine depends on dietary sources as well as remethylation of demethylated methionine (i.e.

Cysteinyl-glycine reduces mucosal proinflammatory cytokine response to fMLP in a parenterally-fed piglet model.

Background: PepT1 transports dietary and bacterial peptides in the gut. We hypothesized that cysteinyl-glycine would ameliorate the inflammatory effect of a bacterial peptide, formyl-methionyl-leucyl-phenylalanine (fMLP), in both sow-fed and parenterally-fed piglets.

Methods: An intestinal perfusion experiment was performed in piglets (N = 12) that were sow-reared or provided with parenteral nutrition (PN) for 4 d.

Betaine is as effective as folate at re-synthesizing methionine for protein synthesis during moderate methionine deficiency in piglets.

Purpose: Both folate and betaine (synthesized from choline) are nutrients used to methylate homocysteine to reform the amino acid methionine following donation of its methyl group; however, it is unclear whether both remethylation pathways are of equal importance during the neonatal period when remethylation rates are high. Methionine is an indispensable amino acid that is in high demand in neonates not only for protein synthesis, but is also particularly important for transmethylation reactions, such as creatine and phosphatidylcholine synthesis. The objective of this study was to determine whether supplementation with folate, betaine, or a combination of both can equally re-synthesize methionine for protein synthesis when dietary methionine is limiting.

Guanidinoacetate is more effective than creatine at enhancing tissue creatine stores while consequently limiting methionine availability in Yucatan miniature pigs.

Creatine (Cr) is an important high-energy phosphate buffer in tissues with a high energy demand such as muscle and brain and is consequently a highly consumed nutritional supplement. Creatine is synthesized via the S-adenosylmethionine (SAM) dependent methylation of guanidinoacetate (GAA) which is not regulated by a feedback mechanism. The first objective of this study was to determine the effectiveness of GAA at increasing tissue Cr stores.

Enterally delivered dipeptides improve small intestinal inflammatory status in a piglet model of intestinal resection.

Unlabelled: PepT1, a di/tripeptide transporter, is preferentially preserved over free amino acid transporters in situations of gut stress. Therefore, our objective was to determine the impact of enterally delivered dipeptide-containing diets on indices of intestinal adaptation in neonatal piglets after intestinal resection.

Methods: Piglets (n = 25, 10 ± 1 d old) underwent an 80% jejuno-ileal resection and were provided 50% of nutritional support as TPN, and 50% as one of five, enteral test diets: 1) a control diet containing free amino acids, or the same diet but with equimolar amounts of free amino acids replaced by 2) alanyl-alanine, 3) alanyl-glutamine, 4) cysteinyl-glycine, or 5) both alanyl-alanine and cysteinyl-glycine.

Enteral arginine partially ameliorates parenteral nutrition-induced small intestinal atrophy and stimulates hepatic protein synthesis in neonatal piglets.

Background: Arginine is an indispensable amino acid in neonates; de novo synthesis of arginine occurs in the small intestine (SI) but is reduced during parenteral nutrition (PN), limiting the arginine available to the mucosa. We assessed the effects of route of intake and dietary concentration of arginine on protein synthesis, superior mesenteric artery (SMA) blood flow, and SI morphology.

Methods: Piglets (n = 18, 14-17 days old) were given complete PN for 3 days to induce SI atrophy, then switched to 1 of 3 treatments: arginine-free PN plus an intragastric (IG) infusion of high arginine (1.

Partitioning of [methyl-3H]methionine to methylated products and protein is altered during high methyl demand conditions in young Yucatan miniature pigs.

Methionine is the main source of methyl groups that are partitioned to synthesize various methylated products including creatine, phosphatidylcholine (PC), and methylated DNA. Whether increased methylation of 1 product can divert methionine from protein synthesis or other methylation products was the aim of this experiment. We used an excess of guanidinoacetate (GAA) to synthesize creatine to create a higher demand for available methyl groups in normal-weight (NW) (n = 10) and intrauterine growth-restricted (IUGR) (n = 10) piglets.

Ontogeny of dipeptide uptake and peptide transporter 1 (PepT1) expression along the gastrointestinal tract in the neonatal Yucatan miniature pig.

The H⁺-coupled transporter, peptide transporter 1 (PepT1), is responsible for the uptake of dietary di- and tripeptides in the intestine. Using an in vivo continuously perfused gut loop model in Yucatan miniature pigs, we measured dipeptide disappearance from four 10 cm segments placed at equidistant sites along the length of the small intestine. Pigs were studied at 1, 2, 3 (suckling) and 6 weeks (post-weaning) postnatal age.

Reduced aluminum contamination decreases parenteral nutrition associated liver injury.

Purpose: Parenteral nutrition-associated cholestasis remains a significant problem, especially for the surgical neonates. Aluminum is a toxic element known to contaminate parenteral nutrition. We hypothesize that parenterally administered aluminum causes liver injury similar to that seen in parenteral nutrition-associated cholestasis.

Proline supplementation to parenteral nutrition results in greater rates of protein synthesis in the muscle, skin, and small intestine in neonatal Yucatan miniature piglets.

Proline and arginine are each indispensable during parenteral feeding due to limited interconversion by an atrophied gut. Commercial amino acid parenteral products designed for neonates contain proline concentrations that differ by almost 4-fold. To assess the adequacy of the lowest concentration of proline provided in commercial total parenteral nutrition (TPN) products, we compared rates of tissue-specific protein synthesis and nitrogen balance in neonatal piglets provided TPN at 2 different proline concentrations.

Glucose tolerance is affected by visceral adiposity and sex, but not birth weight, in Yucatan miniature pigs.

Epidemiological studies have linked small birth weight and lack of breastfeeding to type 2 diabetes mellitus. This study aimed to determine if (i) small birth weight promotes and (ii) suckling prevents the development of adiposity and diabetes biomarkers in a Yucatan miniature pig model. At 3 days of age, the intrauterine growth-restricted (IUGR) piglet (n = 6) was paired with a normal weight (NW), same-sex littermate (n = 6) and fed milk replacer for 4 weeks.

Enteral feeding induces early intestinal adaptation in a parenterally fed neonatal piglet model of short bowel syndrome.

Background: Successful small intestinal (SI) adaptation following surgical resection is essential for optimizing newborn growth and development, but the potential for adaptation is unknown. The authors developed an SI resection model in neonatal piglets supported by intravenous and enteral nutrition.

Methods: Piglets (n = 33, 12-13 days old) were randomized to 80% SI resection with parenteral nutrition feeding (R-PN), 80% SI resection with PN + enteral feeding (R-EN), or sham SI transection with PN + enteral feeding (sham-EN).