High-Protein Exposure during Gestation or Lactation or after Weaning Has a Period-Specific Signature on Rat Pup Weight, Adiposity, Food Intake, and Glucose Homeostasis up to 6 Weeks of Age.

BACKGROUND Early-life nutrition has a programming effect on later metabolic health; however, the impact of exposure to a high-protein (HP) diet is still being investigated. OBJECTIVE This study evaluated the consequences on pup phenotype of an HP diet during gestation and lactation and after weaning. METHODS Wistar rat dams were separated into 2 groups fed an HP (55% protein) or normal protein (NP) (control; 20% protein) isocaloric diet during gestation, and each group subsequently was separated into 2 subgroups that were fed an HP or NP diet during lactation. After weaning, male and female pups from each mother subgroup were separated into 2 groups that were fed either an NP or HP diet until they were 6 wk old. Measurements included weight, food intake, body composition, blood glucose, insulin, glucagon, leptin, insulin-like growth factor I, and lipids. RESULTS Feeding mothers the HP diet during gestation or lactation induced lower postweaning pup weight (gestation diet × time, P < 0.0001; lactation diet × time, P < 0.0001). Regardless of dams' diets, pups receiving HP compared with NP diet after weaning had 7% lower weight (NP, 135.0 ± 2.6 g; HP, 124.4 ± 2.5 g; P < 0.0001), 16% lower total energy intake (NP, 777 ± 14 kcal; HP, 649 ± 13 kcal; P < 0.0001) and 31% lower adiposity (P < 0.0001). Pups receiving HP compared with NP diet after weaning had increased blood glucose, insulin, and glucagon when food deprived (P < 0.0001 for all). The HP compared with the NP diet during gestation induced higher blood glucose in food-deprived rats (NP, 83.2 ± 2.1 mg/dL; HP, 91.2 ± 2.1 mg/dL; P = 0.046) and increased plasma insulin in fed pups receiving the postweaning NP diet (gestation diet × postweaning diet, P = 0.02). CONCLUSION Increasing the protein concentration of the rat dams' diet during gestation, and to a lesser extent during lactation, and of the pups' diet after weaning influenced pup phenotype, including body weight, fat accumulation, food intake, and glucose tolerance at 6 wk of age.

[1]  E. Ota,et al.  Antenatal dietary education and supplementation to increase energy and protein intake. , 2015, The Cochrane database of systematic reviews.

[2]  T. Halldorsson,et al.  Maternal protein intake during pregnancy and offspring overweight 20 y later. , 2014, The American journal of clinical nutrition.

[3]  Annaïg Lan,et al.  High-protein diet modifies colonic microbiota and luminal environment but not colonocyte metabolism in the rat model: the increased luminal bulk connection. , 2014, American journal of physiology. Gastrointestinal and liver physiology.

[4]  C. Gaudichon,et al.  Dietary protein and blood glucose control , 2014, Current opinion in clinical nutrition and metabolic care.

[5]  B. Koletzko,et al.  Lower protein content in infant formula reduces BMI and obesity risk at school age: follow-up of a randomized trial. , 2014, The American journal of clinical nutrition.

[6]  K. Brüssow,et al.  Low and high dietary protein:carbohydrate ratios during pregnancy affect materno-fetal glucose metabolism in pigs. , 2014, The Journal of nutrition.

[7]  S. Hercberg,et al.  Association of nutrition in early life with body fat and serum leptin at adult age , 2013, International Journal of Obesity.

[8]  A. Jamin,et al.  Dietary protein excess during neonatal life alters colonic microbiota and mucosal response to inflammatory mediators later in life in female pigs. , 2013, The Journal of nutrition.

[9]  L. Velázquez-Villegas,et al.  The Dietary Protein/Carbohydrate Ratio Differentially Modifies Lipogenesis and Protein Synthesis in the Mammary Gland, Liver and Adipose Tissue during Gestation and Lactation , 2013, PloS one.

[10]  R. Reimer,et al.  A maternal high-protein diet predisposes female offspring to increased fat mass in adulthood whereas a prebiotic fibre diet decreases fat mass in rats , 2013, British Journal of Nutrition.

[11]  C. Metges,et al.  Enhanced sensitivity of skeletal muscle growth in offspring of mice long-term selected for high body mass in response to a maternal high-protein/low-carbohydrate diet during lactation , 2013, European Journal of Nutrition.

[12]  G. Hooiveld,et al.  Dietary Protein Affects Gene Expression and Prevents Lipid Accumulation in the Liver in Mice , 2012, PloS one.

[13]  V. Tremaroli,et al.  Functional interactions between the gut microbiota and host metabolism , 2012, Nature.

[14]  M. Rogero,et al.  Effects of Two Different Levels of Dietary Protein on Body Composition and Protein Nutritional Status of Growing Rats , 2012, Nutrients.

[15]  C. Metges,et al.  Limited and excess protein intake of pregnant gilts differently affects body composition and cellularity of skeletal muscle and subcutaneous adipose tissue of newborn and weanling piglets , 2012, European Journal of Nutrition.

[16]  B. Koletzko,et al.  Milk protein intake, the metabolic-endocrine response, and growth in infancy: data from a randomized clinical trial. , 2011, The American journal of clinical nutrition.

[17]  A. Beyerlein,et al.  Breastfeeding and body composition in children: will there ever be conclusive empirical evidence for a protective effect against overweight? , 2011, The American journal of clinical nutrition.

[18]  B. Reusens,et al.  Developmental programming of adult obesity and cardiovascular disease in rodents by maternal nutrition imbalance. , 2011, The American journal of clinical nutrition.

[19]  A. Jamin,et al.  The Level of Protein in Milk Formula Modifies Ileal Sensitivity to LPS Later in Life in a Piglet Model , 2011, PloS one.

[20]  P. Even,et al.  Increasing Protein at the Expense of Carbohydrate in the Diet Down-Regulates Glucose Utilization as Glucose Sparing Effect in Rats , 2011, PloS one.

[21]  C. Metges,et al.  Hepatic expression of the GH/JAK/STAT/IGF pathway, acute-phase response signalling and complement system are affected in mouse offspring by prenatal and early postnatal exposure to maternal high-protein diet , 2011, European journal of nutrition.

[22]  C. Metges,et al.  High-protein diet during gestation and lactation affects mammary gland mRNA abundance, milk composition and pre-weaning litter growth in mice. , 2011, Animal : an international journal of animal bioscience.

[23]  A. Jamin,et al.  A high-protein neonatal formula induces a temporary reduction of adiposity and changes later adipocyte physiology. , 2011, American journal of physiology. Regulatory, integrative and comparative physiology.

[24]  D. Tomé,et al.  Colon luminal content and epithelial cell morphology are markedly modified in rats fed with a high-protein diet. , 2010, American journal of physiology. Gastrointestinal and liver physiology.

[25]  O. Sarr,et al.  Prenatal exposure to maternal low or high protein diets induces modest changes in the adipose tissue proteome of newborn piglets. , 2010, Journal of animal science.

[26]  A. Schwiertz,et al.  Microbiota and SCFA in Lean and Overweight Healthy Subjects , 2010, Obesity.

[27]  M. Westerterp-Plantenga,et al.  Dietary protein, weight loss, and weight maintenance. , 2009, Annual review of nutrition.

[28]  K. Swanson,et al.  In utero and postnatal exposure to a high-protein or high-carbohydrate diet leads to differences in adipose tissue mRNA expression and blood metabolites in kittens , 2009, British Journal of Nutrition.

[29]  Peter D Gluckman,et al.  Effect of in utero and early-life conditions on adult health and disease. , 2008, The New England journal of medicine.

[30]  B. Reusens,et al.  Different mechanisms operating during different critical time-windows reduce rat fetal beta cell mass due to a maternal low-protein or low-energy diet , 2007, Diabetologia.

[31]  K. Dear,et al.  Higher maternal dietary protein intake in late pregnancy is associated with a lower infant ponderal index at birth , 2007, European Journal of Clinical Nutrition.

[32]  M. Godes,et al.  High-protein nutrition during pregnancy and lactation programs blood pressure, food efficiency, and body weight of the offspring in a sex-dependent manner. , 2006, American journal of physiology. Regulatory, integrative and comparative physiology.

[33]  T. Roseboom,et al.  The Dutch famine and its long-term consequences for adult health. , 2006, Early human development.

[34]  B. V. van Bon,et al.  Programming of glucose-insulin metabolism in adult sheep after maternal undernutrition. , 2005, American journal of physiology. Regulatory, integrative and comparative physiology.

[35]  T. Harder,et al.  Duration of breastfeeding and risk of overweight: a meta-analysis. , 2005, American journal of epidemiology.

[36]  Steven B Heymsfield,et al.  Waist circumference and abdominal adipose tissue distribution: influence of age and sex. , 2005, The American journal of clinical nutrition.

[37]  Robert W Platt,et al.  Feeding effects on growth during infancy. , 2004, The Journal of pediatrics.

[38]  J. Huneau,et al.  A long-term high-protein diet markedly reduces adipose tissue without major side effects in Wistar male rats. , 2004, American journal of physiology. Regulatory, integrative and comparative physiology.

[39]  F. Nuttall,et al.  Effect of a high-protein, low-carbohydrate diet on blood glucose control in people with type 2 diabetes. , 2004, Diabetes.

[40]  A. Worsley,et al.  Dietary composition of pregnant women is related to size of the baby at birth. , 2004, The Journal of nutrition.

[41]  C. Mølgaard,et al.  Protein intake at 9 mo of age is associated with body size but not with body fat in 10-y-old Danish children. , 2004, The American journal of clinical nutrition.

[42]  P. Even,et al.  A high-protein diet enhances satiety without conditioned taste aversion in the rat , 2003, Physiology & Behavior.

[43]  C. Metges,et al.  Prenatal high protein exposure decreases energy expenditure and increases adiposity in young rats. , 2002, The Journal of nutrition.

[44]  D. Barker.  Fetal and infant origins of adult disease , 2001, Monatsschrift Kinderheilkunde.

[45]  N. Kristensen,et al.  Net portal appearance of volatile fatty acids in sheep intraruminally infused with mixtures of acetate, propionate, isobutyrate, butyrate, and valerate. , 2000, Journal of animal science.

[46]  M. Giannì,et al.  Growth patterns of breast fed and formula fed infants in the first 12 months of life: an Italian study , 1999, Archives of disease in childhood.

[47]  P. Yudkin,et al.  Influence of maternal nutrition on outcome of pregnancy: prospective cohort study , 1999, BMJ.

[48]  Berthold Koletzko,et al.  Breast feeding and obesity: cross sectional study , 1999, BMJ.

[49]  P. G. Reeves.  Components of the AIN-93 diets as improvements in the AIN-76A diet. , 1997, The Journal of nutrition.

[50]  F. Bellisle,et al.  Influence of macronutrients on adiposity development: a follow up study of nutrition and growth from 10 months to 8 years of age. , 1995, International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity.

[51]  B. Lonnerdal,et al.  Energy and protein intakes of breast-fed and formula-fed infants during the first year of life and their association with growth velocity: the DARLING Study. , 1993, The American journal of clinical nutrition.

[52]  P. Clifton,et al.  Influence of gender, body mass index, and age on response of plasma lipids to dietary fat plus cholesterol. , 1992, Arteriosclerosis and thrombosis : a journal of vascular biology.

[53]  P. Mortensen,et al.  Degradation of amino acids to short-chain fatty acids in humans. An in vitro study. , 1988, Scandinavian journal of gastroenterology.

[54]  R. Blazquez,et al.  The effect of a high-protein diet on plasma glucose concentration, insulin sensitivity and plasma insulin in rats. , 1970, The Journal of endocrinology.

[55]  Evelyn Witkin,et al.  The Journal of Clinical Investigation , 2016 .

[56]  C. Aiken,et al.  Sex differences in developmental programming models. , 2013, Reproduction.

[57]  H. Yoshimatsu,et al.  The effects of branched-chain amino acid granules on the accumulation of tissue triglycerides and uncoupling proteins in diet-induced obese mice. , 2011, Endocrine journal.

[58]  S. Sebert,et al.  Nutritional programming of the metabolic syndrome , 2009, Nature Reviews Endocrinology.