CONTEXT: The protective effect of breast-feeding against later obesity may be explained by the lower protein content compared with formula milk. However, the metabolic mechanisms remain unknown. OBJECTIVE: We studied the metabolic response to a higher or lower protein supply in infancy. DESIGN AND SETTING: The Childhood Obesity Project study is a double-blind, randomized, multicenter intervention trial. Infants were randomized to receive a higher (HP) or lower protein (LP) content infant formula or were breast-fed. PATIENTS AND INTERVENTIONS: Plasma samples of 691 infants who received formula milk with different protein content (HP, 2.05 g per 100 mL; LP, 1.25 g per 100 mL) or were breast-fed were collected. MAIN OUTCOME MEASURES: Changes in plasma amino acid and acylcarnitine concentrations of 6-month-old infants according to different dietary protein supply were determined by liquid chromatography coupled to tandem mass spectrometry. RESULTS: Twenty-nine metabolites differed significantly between the formula groups. Branched-chain amino acids (BCAAs) were the most discriminant metabolites. Their degradation products, the short-chain acylcarnitines C3, C4, and C5, were also significantly elevated in the HP group. A breakpoint analysis confirmed that with increasing BCAAs, the ratio between acylcarnitines and BCAAs decreases. Long-chain acylcarnitines were decreased in HP infants. CONCLUSIONS: BCAAs seem to play a pivotal role in the effect of a high-protein diet on β-oxidation and fat storage. We provide new evidence for a possible saturation of the BCAA degradation pathway that may represent the mechanism by which high-protein intake affects the metabolic regulation. Moreover, it appears to inhibit the initial step of the β-oxidation, thus leading to high early weight gain and body fat deposition.
RCT Entities:
CONTEXT: The protective effect of breast-feeding against later obesity may be explained by the lower protein content compared with formula milk. However, the metabolic mechanisms remain unknown. OBJECTIVE: We studied the metabolic response to a higher or lower protein supply in infancy. DESIGN AND SETTING: The Childhood Obesity Project study is a double-blind, randomized, multicenter intervention trial. Infants were randomized to receive a higher (HP) or lower protein (LP) content infant formula or were breast-fed. PATIENTS AND INTERVENTIONS: Plasma samples of 691 infants who received formula milk with different protein content (HP, 2.05 g per 100 mL; LP, 1.25 g per 100 mL) or were breast-fed were collected. MAIN OUTCOME MEASURES: Changes in plasma amino acid and acylcarnitine concentrations of 6-month-old infants according to different dietary protein supply were determined by liquid chromatography coupled to tandem mass spectrometry. RESULTS: Twenty-nine metabolites differed significantly between the formula groups. Branched-chain amino acids (BCAAs) were the most discriminant metabolites. Their degradation products, the short-chain acylcarnitines C3, C4, and C5, were also significantly elevated in the HP group. A breakpoint analysis confirmed that with increasing BCAAs, the ratio between acylcarnitines and BCAAs decreases. Long-chain acylcarnitines were decreased in HP infants. CONCLUSIONS:BCAAs seem to play a pivotal role in the effect of a high-protein diet on β-oxidation and fat storage. We provide new evidence for a possible saturation of the BCAA degradation pathway that may represent the mechanism by which high-protein intake affects the metabolic regulation. Moreover, it appears to inhibit the initial step of the β-oxidation, thus leading to high early weight gain and body fat deposition.
Authors: Jessica L Saben; Clark R Sims; Lindsay Pack; Renny Lan; Elisabet Børsheim; Aline Andres Journal: Pediatr Obes Date: 2021-12-16 Impact factor: 3.910
Authors: Christian Hellmuth; Olaf Uhl; Hans Demmelmair; Maria Grunewald; Renata Auricchio; Gemma Castillejo; Ilma R Korponay-Szabo; Isabel Polanco; María Roca; Sabine L Vriezinga; Katharina J Werkstetter; Berthold Koletzko; M Luisa Mearin; Franca F Kirchberg Journal: PLoS One Date: 2018-06-01 Impact factor: 3.240
Authors: Aneesia Varkey; Sarita Devi; Arpita Mukhopadhyay; Namrata G Kamat; Maria Pauline; Madan Dharmar; Roberta R Holt; Lindsay H Allen; Tinku Thomas; Carl L Keen; Anura V Kurpad Journal: Clin Nutr Date: 2020-02-24 Impact factor: 7.324
Authors: Christian Hellmuth; Franca Fabiana Kirchberg; Nina Lass; Ulrike Harder; Wolfgang Peissner; Berthold Koletzko; Thomas Reinehr Journal: J Diabetes Res Date: 2015-12-21 Impact factor: 4.011