Hypothalamus integrity and appetite regulation in low birth weight rats reared artificially on a high-protein milk
Bérengère Coupé1, Eloïse Delamaire, Christine Hoebler
1INRA, Laboratoire de Physiologie des Adaptations Nutritionnelles, Université de Nantes, Nantes atlantique, CHU Hôtel Dieu, place Alexis Ricordeau, France.
Insights
High-protein (HP) milk formula for low birth weight (LBW) infants may alter appetite regulation and energy homeostasis in adulthood. This study found HP milk led to increased weight gain and altered feeding behaviors in adult rats.
Area of Science:
- Neuroscience
- Developmental Biology
- Metabolic Research
Background:
- High-protein (HP) milk formulas are common for low birth weight (LBW) infants to promote growth and cognitive development.
- Early life HP intake is indirectly linked to later-life obesity.
- The impact of HP milk on hypothalamic appetite regulation in LBW infants is not fully understood.
Purpose of the Study:
- To investigate the effects of early postnatal high-protein (HP) milk supplementation in low birth weight (LBW) rat pups on hypothalamic appetite neuronal pathways.
- To assess the long-term consequences on energy homeostasis and feeding behavior in adulthood.
Main Methods:
- LBW rat pups received either normal protein (NP) or high protein (HP) milk formula via gastrostomy tube from postnatal day 5.
- Rats were weaned to a standard diet at postnatal day 21.
- Adult rats were assessed for body weight, plasma markers (insulin, leptin, triglycerides), hypothalamic gene expression, and feeding behavior.
Main Results:
- HP-fed adult rats exhibited greater weight gain, elevated plasma insulin, leptin, and triglycerides compared to NP-fed rats.
- Hypothalamic gene expression for cell proliferation and neurotrophin markers was higher in HP-fed rats.
- Adult feeding behaviors, including satiety period and meal patterns, differed between HP and NP groups, despite similar arcuate nucleus projections.
Conclusions:
- Early postnatal HP milk supplementation in LBW rats influences adult body weight, metabolic markers, and feeding behaviors.
- Molecular changes in the hypothalamus suggest altered neural development pathways.
- These findings highlight potential long-term metabolic and neural consequences of HP milk for LBW infants.
Abstract:
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.
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