Related Experiment Video
Updated: Jul 7, 2025
Increasing Pulmonary Artery Pulsatile Flow Improves Hypoxic Pulmonary Hypertension in Piglets
Published on: May 11, 2015
Pulsatile Leucine Administration during Continuous Enteral Feeding Enhances Skeletal Muscle Mechanistic Target of
Marko Rudar1, Agus Suryawan2, Hanh V Nguyen2
1Department of Animal Sciences, Auburn University, Auburn, AL, United States.
Insights
Intravenous leucine pulses enhance muscle protein synthesis in preterm pigs. Higher leucine doses are needed compared to term-born pigs to achieve optimal anabolic responses.
Area of Science:
- Nutritional biochemistry
- Skeletal muscle physiology
- Neonatal nutrition
Background:
- Continuous feeding is suboptimal for muscle anabolism but necessary for preterm infants.
- Previous studies showed intermittent leucine pulses stimulate muscle protein synthesis in term-born pigs.
Purpose of the Study:
- To investigate the impact of intravenous leucine pulses on mTORC1 activation and protein synthesis in preterm pigs under continuous feeding.
- To determine the optimal leucine dosage for anabolic response in this population.
Main Methods:
- Preterm pigs were continuously fed and received intravenous pulses of alanine or leucine (L1x, L2x) or intermittent feeding (INT).
- Muscle protein synthesis was measured using L-[2H5-ring]Phenylalanine.
- Signaling pathways (insulin, amino acid, translation initiation) were analyzed via Western blot.
Main Results:
- Higher plasma leucine concentrations were observed with increased leucine pulse doses (L2x vs. L1x and ALA).
- Muscle protein synthesis was significantly enhanced in the L2x group compared to ALA and L1x groups.
- Signaling pathway activation correlated with protein synthesis rates, with mTORC1 playing a key role.
Conclusions:
- Intravenous leucine pulses effectively stimulate mTORC1 activity and protein synthesis in the skeletal muscle of continuously fed preterm pigs.
- The required leucine dosage for optimal response in preterm pigs is higher than in term-born pigs.
Background:
Continuous feeding does not elicit an optimal anabolic response in skeletal muscle but is required for some preterm infants. We reported previously that intermittent intravenous pulses of leucine (Leu; 800 μmol Leu·kg-1·h-1 every 4 h) to continuously fed pigs born at term promoted mechanistic target of rapamycin complex 1 (mTORC1) activation and protein synthesis in skeletal muscle.
Objectives:
The aim was to determine the extent to which intravenous Leu pulses activate mTORC1 and enhance protein synthesis in the skeletal muscle of continuously fed pigs born preterm.
Methods:
Pigs delivered 10 d preterm was advanced to full oral feeding >4 d and then assigned to 1 of the following 4 treatments for 28 h: 1) ALA (continuous feeding; pulsed with 800 μmol alanine·kg-1·h-1 every 4 h; n = 8); 2) L1× (continuous feeding; pulsed with 800 μmol Leu·kg-1·h-1 every 4 h; n = 7); 3) L2× (continuous feeding; pulsed with 1600 μmol Leu·kg-1·h-1 every 4 h; n = 8); and 4) INT (intermittent feeding every 4 h; supplied with 800 μmol alanine·kg-1 per feeding; n = 7). Muscle protein synthesis rates were determined with L-[2H5-ring]Phenylalanine. The activation of insulin, amino acid, and translation initiation signaling pathways were assessed by Western blot.
Results:
Peak plasma Leu concentrations were 134% and 420% greater in the L2× compared to the L1× and ALA groups, respectively (P < 0.01). Protein synthesis was greater in the L2× than in the ALA and L1× groups in both the longissimus dorsi and gastrocnemius muscles (P < 0.05) but not different from the INT group (P > 0.10). Amino acid signaling upstream and translation initiation signaling downstream of mTORC1 largely corresponded to the differences in protein synthesis.
Conclusions:
Intravenous Leu pulses potentiate mTORC1 activity and protein synthesis in the skeletal muscles of continuously fed preterm pigs, but the amount required is greater than in pigs born at term.
Related Concept Videos
01:22PI3K/mTOR/AKT Signaling Pathway
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...