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            <funder>This work was supported by the Indo-French Centre for the Promotion of Advanced Research (IFCPAR/CEFIPRA) and the AlimH Division of the French Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE).</funder>
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                <title level="j">Journal of Nutrition</title>
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                  <date type="datePub">2025-08</date>
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                <term xml:lang="en">amino acid deficiency</term>
                <term xml:lang="en">amino acid supplementation</term>
                <term xml:lang="en">energy metabolism</term>
                <term xml:lang="en">protein malnutrition</term>
                <term xml:lang="en">supplementation</term>
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              <p>BackgroundInadequate protein intake in early life is associated with both growth retardation and a higher risk of metabolic syndrome in later life.ObjectiveThis study aimed to evaluate the effects on energy metabolism of protein or indispensable amino acids (IAAs; lysine, threonine, and methionine) supplementation following a deficiency in growing rats.MethodsSixty Wistar Han male rats were fed a control (20% protein by energy content), protein-deficient (P5, 5% protein by energy content), or lysine, threonine, or methionine-deficient diet (L25, T25, and M25, respectively; 25% of the IAA requirement) for 3 wk and thereafter were supplemented for 3 wk with the deficient IAA or protein to reach 100% of the IAA (T100, L100, and M100, respectively) or protein requirement (P20). Body weight (BW) and relative food intake (rFI) were measured daily. Body composition, nasoanal length (NAL), energy expenditure, and plasma fibroblast growth factor 21 were measured at the end of the deficiency and supplementation phases. Data were analyzed using 1-way or mixed-model ANOVA and Bonferonni tests for multiple comparisons.ResultsAll deficient diets induced growth retardation [lower BW, lean body mass (LBM), and NAL], with threonine deficiency having the most severe effect (60% lower BW of control; P &amp;lt; 0.001). Supplementation induced a resumption of growth, but BW and LBM remained lower (15%–35% for BW and 69%– 84% for LBM of control; P &amp;lt; 0.001). Despite increased rFI, no excess adiposity was observed postsupplementation in P20 and T100 groups, likely due to increased energy expenditure (P &amp;lt; 0.001). In L100 and M100 groups, rFI increased (by 35% and 30%, respectively; P &amp;lt; 0.001) without a corresponding rise in energy expenditure. Fibroblast growth factor 21 was inversely associated with the protein and IAA statuses during both deficiency and supplementation (P &amp;lt; 0.001).ConclusionsThese findings highlight the distinct roles of individual IAAs in growth and metabolic recovery and suggest that targeted IAA supplementation may improve nutritional interventions.</p>
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          <orgName>Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement</orgName>
          <orgName type="acronym">INRAE</orgName>
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