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Lysine Dipeptide Enhances Gut Structure and Whole-Body Protein Synthesis in Neonatal Piglets with Intestinal Atrophy
Dalshini Kirupananthan1, Robert F Bertolo1, Janet A Brunton1
1Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL, Canada.
Insights
Enteral feeding of lysine as a dipeptide (Lys-Lys) improved gut structure and protein synthesis in piglets with parenteral nutrition-induced atrophy. This suggests leveraging peptide transporter-1 (PepT1) can enhance nutrient absorption in compromised neonatal guts.
Area of Science:
- Neonatal Nutrition
- Gastroenterology
- Pediatric Research
Background:
- Parenteral nutrition (PN) is essential for preterm infants but can cause gut atrophy and increase infection risk.
- Peptide transporter-1 (PepT1) remains active during gut atrophy, offering a potential route for nutrient delivery.
- Dipeptide forms of amino acids may be more effectively absorbed than free amino acids in atrophic guts.
Purpose of the Study:
- To investigate the effects of enteral refeeding with lysine as a dipeptide (Lys-Lys) versus free L-lysine in piglets with PN-induced intestinal atrophy.
- To determine the structural and functional impact of dipeptide lysine on gut health and protein synthesis.
Main Methods:
- Yucatan miniature piglets were fed parenterally for 4 days to induce gut atrophy.
- Piglets were then refed enterally with lysine as Lys-Lys, free L-lysine, or Lys-Lys with a PepT1 inhibitor (glycyl-sarcosine).
- Measurements included gut structure (villus height, mucosal weight), protein synthesis, and inflammation markers.
Main Results:
- Lys-Lys supplementation significantly increased villus height, mucosal weight, and free lysine concentration compared to free lysine.
- Whole-body protein synthesis was greater with Lys-Lys compared to free lysine.
- Lys-Lys reduced gut inflammation (myeloperoxidase activity) and PepT1 inhibition abolished the benefits, confirming PepT1 mediation.
Conclusions:
- Enteral feeding of lysine as a dipeptide enhances intestinal structure and protein synthesis in neonatal piglets with gut atrophy.
- Exploiting PepT1-mediated nutrient uptake may be a viable strategy to mitigate adverse effects of PN and reintroduce enteral nutrition.
- This approach holds promise for improving outcomes in compromised neonatal gastrointestinal systems.
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.
Objectives:
In Yucatan miniature piglets with PN-induced intestinal atrophy, we sought to determine the structural and functional effects of enteral refeeding with lysine as a dipeptide, compared to free L-lysine.
Methods:
Piglets aged 7-8 days were PN-fed for 4 days to induce intestinal atrophy, then were refed with enteral diets with equimolar lysine supplied as lysyl-lysine (Lys-Lys; n = 7), free lysine (n = 7), or Lys-Lys with glycyl-sarcosine (n = 6; to determine whether competitive inhibition of Lys-Lys uptake would abolish PepT1-mediated effects). The diets provided lysine at 75% of the requirement and were gastrically delivered for a total of 18 hours. Whole-body and tissue-specific protein synthesis, as well as indices for gut structure and barrier function, were measured.
Results:
The villus height, mucosal weight, and free lysine concentration were higher in the Lys-Lys group compared to the other 2 groups (P < 0.05). Lysyl-lysine led to greater whole-body protein synthesis compared to free lysine (P < 0.05). Mucosal myeloperoxidase activity was lower in the Lys-Lys group (P < 0.05), suggesting less inflammation. The inclusion of glycyl-sarcosine with Lys-Lys abolished the dipeptide effects on whole-body and tissue-specific protein synthesis (P < 0.05), suggesting that improved lysine availability was mediated by PepT1.
Conclusions:
Improved intestinal structure and whole-body protein synthesis suggests that feeding strategies designed to exploit PepT1 may help to avoid adverse effects when enteral nutrition is reintroduced into the compromised guts of neonatal piglets.
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