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Protein or Indispensable Amino Acid Supplementation After Deficiency Partially Restored Growth and Did Not Induce Higher Adiposity in Growing Rats.

Groups and Associations Roisné-Hamelin, Gaëtan; Cansell, Céline; Chaumontet, Catherine; Devi, Sarita; Tomé, Daniel; Kurpad, Anura; Even, Patrick C.; Blais, Anne; Piedcoq, Julien; Gaudichon, Claire; Azzout-Marniche, Dalila
The Journal of Nutrition 2025

BACKGROUND: Inadequate protein intake in early life is associated with both growth retardation and a higher risk of metabolic syndrome in later life.  OBJECTIVE: This 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. METHODS: Sixty 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. RESULTS: All 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 < 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 < 0.001). Despite increased rFI, no excess adiposity  was observed postsupplementation in P20 and T100 groups, likely due to increased  energy expenditure (P < 0.001). In L100 and M100 groups, rFI increased (by 35%  and 30%, respectively; P < 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 < 0.001).  CONCLUSIONS: These findings highlight the distinct roles of individual IAAs in  growth and metabolic recovery and suggest that targeted IAA supplementation may  improve nutritional interventions.