Perinatal protein restriction affects milk free amino acid and fatty acid profile in lactating rats: potential role on pup growth and metabolic status.
Perinatal undernutrition affects not only fetal and neonatal growth but also adult health outcome, as suggested by the metabolic imprinting concept. Although maternal milk is the only channel through which nutrients are transferred from mother to offspring during the postnatal period, the impact of maternal undernutrition on milk composition is poorly understood. The present study investigates, in a rat model of nutritional programming, the effects of feeding an isocaloric, low-protein diet throughout gestation and lactation on milk composition and its possible consequences on offspring's growth and metabolic status. We used an integrated methodological approach that combined targeted analyses of macronutrients, free amino acid and fatty acid content throughout lactation, with an untargeted mass-spectrometric-based metabolomic phenotyping. Whereas perinatal dietary protein restriction failed to alter milk protein content, it dramatically decreased the concentration of most free amino acids at the end of lactation. Interestingly, a decrease of several amino acids involved in insulin secretion or gluconeogenesis was observed, suggesting that maternal protein restriction during the perinatal period may impact the insulinotrophic effect of milk, which may, in turn, account for the slower growth of the suckled male offspring. Besides, the decrease in sulfur amino acids may alter redox status in the offspring. Maternal undernutrition was also associated with an increase in milk total fatty acid content, with modifications in their pattern. Altogether, our results show that milk composition is clearly influenced by maternal diet and suggest that alterations in milk composition may play a role in offspring growth and metabolic programming.
INRA, UMR1280, Physiologie des Adaptations Nutritionnelles, Institut des Maladies de l'Appareil Digestif (IMAD), Centre de Recherche en Nutrition Humaine Ouest (CRNH), Nantes, France; LUNAM, Institut des Maladies de l'Appareil Digestif (IMAD), Centre de Recherche en Nutrition Humaine Ouest (CRNH), Nantes, France.
Aurore
A
Martin Agnoux
LUNAM, Oniris, Laboratoire d'Etude des Résidus et Contaminants dans les Aliments (LABERCA), USC INRA 1329, Nantes, France.
Jean-Philippe
JP
Antignac
INRA, UMR1280, Physiologie des Adaptations Nutritionnelles, Institut des Maladies de l'Appareil Digestif (IMAD), Centre de Recherche en Nutrition Humaine Ouest (CRNH), Nantes, France; LUNAM, Institut des Maladies de l'Appareil Digestif (IMAD), Centre de Recherche en Nutrition Humaine Ouest (CRNH), Nantes, France.
Clair-Yves
CY
Boquien
INRA, UMR1280, Physiologie des Adaptations Nutritionnelles, Institut des Maladies de l'Appareil Digestif (IMAD), Centre de Recherche en Nutrition Humaine Ouest (CRNH), Nantes, France; LUNAM, Institut des Maladies de l'Appareil Digestif (IMAD), Centre de Recherche en Nutrition Humaine Ouest (CRNH), Nantes, France.
Agnes
A
David
INRA, UMR1280, Physiologie des Adaptations Nutritionnelles, Institut des Maladies de l'Appareil Digestif (IMAD), Centre de Recherche en Nutrition Humaine Ouest (CRNH), Nantes, France; LUNAM, Institut des Maladies de l'Appareil Digestif (IMAD), Centre de Recherche en Nutrition Humaine Ouest (CRNH), Nantes, France.
Emmanuelle
E
Desnots
INRA, UMR1280, Physiologie des Adaptations Nutritionnelles, Institut des Maladies de l'Appareil Digestif (IMAD), Centre de Recherche en Nutrition Humaine Ouest (CRNH), Nantes, France; LUNAM, Institut des Maladies de l'Appareil Digestif (IMAD), Centre de Recherche en Nutrition Humaine Ouest (CRNH), Nantes, France.
Veronique
V
Ferchaud-Roucher
INRA, UMR1280, Physiologie des Adaptations Nutritionnelles, Institut des Maladies de l'Appareil Digestif (IMAD), Centre de Recherche en Nutrition Humaine Ouest (CRNH), Nantes, France; LUNAM, Institut des Maladies de l'Appareil Digestif (IMAD), Centre de Recherche en Nutrition Humaine Ouest (CRNH), Nantes, France.
Dominique
D
Darmaun
INRA, UMR1280, Physiologie des Adaptations Nutritionnelles, Institut des Maladies de l'Appareil Digestif (IMAD), Centre de Recherche en Nutrition Humaine Ouest (CRNH), Nantes, France; LUNAM, Institut des Maladies de l'Appareil Digestif (IMAD), Centre de Recherche en Nutrition Humaine Ouest (CRNH), Nantes, France.
Patricia
P
Parnet
INRA, UMR1280, Physiologie des Adaptations Nutritionnelles, Institut des Maladies de l'Appareil Digestif (IMAD), Centre de Recherche en Nutrition Humaine Ouest (CRNH), Nantes, France; LUNAM, Institut des Maladies de l'Appareil Digestif (IMAD), Centre de Recherche en Nutrition Humaine Ouest (CRNH), Nantes, France. Electronic address: Marie-Cecile.Alexandre-Gouabau@univ-nantes.fr.
Marie-Cécile
MC
Alexandre-Gouabau
D050154:Adiposity; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D000833:Animals, Suckling; D018753:Diet, Protein-Restricted / Q000009:adverse effects*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D047109:Fetal Development; D006130:Growth Disorders / Q000209:etiology; D007774:Lactation / Q000378:metabolism*; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D008659:Metabolic Diseases / Q000209:etiology; D055432:Metabolomics / Q000379:methods; D008892:Milk / Q000378:metabolism*; D008894:Milk Proteins / Q000008:administration & dosage / Q000032:analysis / Q000096:biosynthesis; D018384:Oxidative Stress; D011247:Pregnancy; D011897:Random Allocation; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D005227:Fatty Acids; D008894:Milk Proteins
Fatty acid; Free amino acid; Maternal dietary protein restriction; Metabolome; Milk composition; Organ growth