Amino Acid Signaling in Skeletal Muscle Is Blunted by Prematurity in a Piglet Model
Bibliographic record
Abstract
BACKGROUND: Preterm (PT) infants are at increased risk for reduced postnatal lean mass accretion. We established that the feeding-induced stimulation of protein synthesis in skeletal muscle is blunted in piglets born PT compared with those born at term. OBJECTIVES: We evaluated the extent to which key components of the amino acid-sensing pathways that regulate mechanistic target of rapamycin complex 1 (mTORC1) activation contribute to anabolic resistance in skeletal muscle of piglets born PT compared with those born term. METHODS: Piglets delivered by cesarean section 10 d PT (n = 23) or at term (n = 22) were administered total parenteral nutrition for 3 d. On day 4, euinsulinemic-euaminoacidemic-euglycemic (FAST group), hyperinsulinemic-euaminoacidemic-euglycemic (INS group), or euinsulinemic-hyperaminoacidemic-euglycemic (AA group) clamps were performed for 2 h. Abundances and activation of amino acid signaling components in skeletal muscle were analyzed by immunoblotting. RESULTS: Abundances of amino acid transporters LAT1/SLC7A5 (leucine), SLC38A9 (arginine), and SNAT2/SLC38A2 (glutamine) were unaffected by prematurity. Sestrin1- and Sestrin2-GATOR2 abundances were reduced (P < 0.05) by AA, consistent with leucine-induced dissociation of these inhibitory complexes; prematurity blunted this effect for Sestrin1-GATOR2 (P < 0.05). SAR1B, but not LARS-mTOR, leucine-sensor abundances were lower in PT than term animals (P < 0.05). TARS2 (threonine) and RAB1A (branched-chain amino acid) sensor abundances were lower in PT (P < 0.05). Arginine (CASTOR1-GATOR2), methionine (SAMTOR-GATOR1), and glutamine (ARF1) sensor abundances were unaffected by prematurity. AA-induced formations of RagA- and RagC-mTOR complexes were attenuated in PT compared with term piglets (P < 0.05). Both AA and INS stimulated mTORC1 phosphorylation, but these effects were blunted by prematurity. CONCLUSIONS: PT birth impairs the abundance and activation of multiple amino acid-sensing components upstream of mTORC1 in skeletal muscle. This disruption attenuates amino acid-induced mTORC1-dependent translation initiation and protein synthesis and likely contributes to the anabolic resistance, reduced lean mass, and extrauterine growth faltering frequently observed in premature infants.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".