High protein intake in neonatal period induces glomerular hypertrophy and sclerosis in adulthood in rats born with IUGR.

BACKGROUND: Intrauterine growth restriction (IUGR) and postnatal nutrition are risk factors for cardiovascular and renal diseases in both humans and animals. The long-term renal effects of protein intake early in life remain unknown. The objective was to evaluate the effects of a neonatal feeding with high protein (HP) milk on renal functions and structure in IUGR male rats. METHODS: Maternal gestational low protein diet was used to produce IUGR. At day 5, IUGR pups were gastrostomized in the "pup-in-the cup" model and received either normal protein (NP) milk or HP (+50% protein content) milk until day 21. After weaning, the animals were fed the same standard diet. Renal functions and structure were assessed at postnatal day 18 (D18) and in adult offspring. RESULTS: During the preweaning period, the postnatal weight gain between the two groups was unaffected. On D18, kidneys from HP offspring were heavier with significant glomerular hypertrophy (+40%, P < 0.05). HP diet was associated with significant proteinuria and glomerulosclerosis (+49%, P < 0.05). Glomerular number was unaltered. CONCLUSION: Neonatal HP feeding following IUGR affects renal functions and structure at adulthood. These alterations may result from a single nephron glomerular hyperfiltration.

Long term metabolic impact of high protein neonatal feeding: a preliminary study in male rat pups born with a low birth weight.

BACKGROUND & AIMS: Nutrition received in early life may impact adult health. The aim of the study was to determine whether high protein feeding in neonatal period would have long term metabolic effects in an animal model of low birth weight infants. METHODS: Male rat pups born from dams receiving a low protein diet during gestation were separated from their mothers, and equipped with gastrostomy tubes to receive as their sole feeding a milk formula of either adequate protein (AP; n = 14; 8.7 g protein/dL; total energy: 155 kcal/100 g), or high protein content (HP; n = 14; 13.0 g protein/dL; total energy: 171 kcal/100 g) between the 7th (D7) and 21st day (D21) of life. Rats were then weaned to standard chow until sacrificed at adulthood. RESULTS: At D18, HP feeding was associated with higher estimated rates of protein turnover (p = 0.007) and synthesis (p = 0.051), as assessed using l-[U-(13)C]valine infusion. HP milk feeding in early life was associated with an increase in weight gain from puberty through adulthood, along with an increase in food intake, serum insulin (179 ± 58 vs. 55 ± 7 pmol/L; means ± SE), pancreatic ß-cell number, plasma triglycerides (95 ± 8 vs. 73 ± 9 mg/dL), serum leptin (9.7 ± 1.0 vs. 5.5 ± 1.2 ng/mL), mesenteric fat mass, and adipocyte size. CONCLUSIONS: In an animal model of low birth weight infants, high protein neonatal feeding may have a lasting effect on fat and glucose metabolism, potentially leading to "metabolic syndrome" in adulthood.

Hypothalamus integrity and appetite regulation in low birth weight rats reared artificially on a high-protein milk formula.

High-protein (HP) milk formulas are routinely used in infants born with a low birth weight (LBW) to enhance growth and ensure a better verbal IQ development. Indirect evidence points to a link between an HP intake during early life and the prevalence of obesity in later life. We hypothesized that HP milk supplementation to LBW pups during early postnatal life would impact hypothalamic appetite neuronal pathways development with consequences, at adulthood, on energy homeostasis regulation. Rat pups born with a LBW were equipped with gastrostomy tubes on the fifth day of life. They received a milk formula with either normal protein (NP, 8.7 g protein/dl) or high protein content (HP; 13.0 g protein/dl) and were subsequently weaned to a standard, solid diet at postnatal day 21. Rats that had been fed HP content milk gained more weight at adulthood associated with an increase of plasma insulin, leptin and triglycerides concentrations compared to NP rats. Screening performed on hypothalamus in development from the two groups of rats identified higher gene expression for cell proliferation and neurotrophin markers in HP rats. Despite these molecular differences, appetite neuronal projections emanating from the arcuate nucleus did not differ between the groups. Concerning feeding behavior at adulthood, rats that had been fed HP or NP milk exhibited differences in the satiety period, resting postprandial duration and nocturnal meal pattern. The consequences of HP milk supplementation after LBW will be discussed in regard to neural development and metabolic anomalies.

Changes in mammary uptake and metabolic fate of glucose with once-daily milking and feed restriction in dairy cows.

The aim of this review is to better understand the regulation of milk yield in response to once-daily milking and feed restriction. Glucose is the principal precursor for the synthesis of lactose (a major osmotic agent in milk), and participates in determining the milk volume produced. When applying these two breeding factors, reductions in milk yield are associated with a reduction in milk lactose yield and in the arterial flow of glucose, due to a decrease in the mammary blood flow. The ability of the udder to extract glucose is altered with once-daily milking but not necessarily with feed restriction. Lactose synthesis is down-regulated in response to once-daily milking and feed restriction but the percentage of the extracted glucose which is converted into lactose is differently affected in response to treatments. No marked change is observed with once daily milking whereas this would be increased with feed restriction and in contrast, depressed with fasting.