Hypothalamic nuclei are malformed in weanling offspring of low protein malnourished rat dams
A Plagemann1, T Harder, A Rake
1Institute of Experimental Endocrinology, Humboldt University Medical School (Charité), 10098 Berlin, Germany.
Insights
Maternal low protein malnutrition in rats leads to altered hypothalamic development in offspring, affecting body weight and metabolism regulation. These changes suggest long-term risks for metabolic disorders.
Area of Science:
- Neuroscience
- Developmental Biology
- Metabolic Research
Background:
- Maternal malnutrition during gestation and lactation (LP) is a model for perinatal growth retardation.
- Growth retardation is linked to later-life diabetic and cardiovascular issues, but mechanisms are unclear.
- Hypothalamic nuclei regulate food intake, body weight, and metabolism.
Purpose of the Study:
- To investigate the effects of maternal low protein (LP) diet on hypothalamic development in offspring.
- To examine the impact on regulators of body weight and metabolism at weaning.
Main Methods:
- Rats were fed either a low protein (8%) or control (17%) diet during gestation and lactation.
- Offspring were assessed at weaning (day 20) for body weight, glucose, insulin, and hypothalamic neuronal organization.
- Specific hypothalamic nuclei (ventromedial, paraventricular, arcuate, lateral, dorsomedial) were analyzed for volume and neuronal density (Nissl, Neuropeptide Y, Galanin, Cholecystokinin-8S).
Main Results:
- LP offspring exhibited lower body weight, hypoglycemia, and hypoinsulinemia compared to controls.
- Increased relative volume and neuronal density were observed in the ventromedial and paraventricular hypothalamic nuclei of LP offspring.
- LP offspring showed reduced Neuropeptide Y-positive neurons in the arcuate nucleus and Galanin-positive neurons in the paraventricular nucleus.
Conclusions:
- Maternal low protein malnutrition alters hypothalamic development in offspring.
- These hypothalamic changes may contribute to long-term metabolic dysregulation and increased risk of disease.
Abstract:
Maternal low protein malnutrition during gestation and lactation (LP) is an animal model frequently used for the investigation of long-term deleterious consequences of perinatal growth retardation. Both perinatal malnutrition and growth retardation at birth are risk factors for diabetic and cardiovascular disturbances in later life. The pathophysiologic mechanisms responsible are unknown. Hypothalamic nuclei are decisively involved in the central nervous regulation of food intake, body weight and metabolism. We investigated effects of a low protein diet (8% protein; control diet, 17% protein) during gestation and lactation in rat dams on the organization of hypothalamic regulators of body weight and metabolism in the offspring at weaning (d 20 of life). LP offspring had significantly lower body weight than control offspring (CO; P: < 0.001), associated with hypoglycemia and hypoinsulinemia (P: < 0. 005) on d 20 of life. This was accompanied by a greater relative volume of the ventromedial hypothalamic nucleus (P: < 0.01) and a greater numerical density of Nissl-stained neurons in this nucleus (P: < 0.01) as well as in the paraventricular hypothalamic nucleus (PVN; P: < 0.001). In contrast, no significant differences in neuronal densities were observed generally in the lateral hypothalamic area, arcuate hypothalamic nucleus (ARC), and dorsomedial hypothalamic nucleus between LP offspring and CO offspring. On the other hand, LP offspring displayed fewer neurons immunopositive for neuropeptide Y in the ARC (P: < 0.05), whereas in the PVN, lower neuronal densities of neurons immunopositive for galanin were found in LP offspring compared with CO offspring (P: < 0.001). On the contrary, in the PVN, no significant group difference in the numerical density of cholecystokinin-8S-positive neurons was present. A long-term effect of these specific hypothalamic alterations on body weight and metabolism in LP offspring during later life is suggested.
