Perinatal elevation of hypothalamic insulin, acquired malformation of hypothalamic galaninergic neurons, and syndrome X-like alterations in adulthood of neonatally overfed rats

• Published in: Brain research Vol. 836; no. 1; pp. 146 - 155
• Main Authors: Plagemann, Andreas, Harder, Thomas, Rake, Annett, Voits, Mechthild, Fink, Heidrun, Rohde, Wolfgang, Dörner, Günter
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 31.07.1999; Amsterdam Elsevier; New York, NY
• Subjects: Animals; Animals, Newborn; Biological and medical sciences; Body Weight - physiology; Cell Differentiation - physiology; Early overnutrition; Feeding Behavior - physiology; Female; Galanin; Galanin - analysis; Hypothalamus; Hypothalamus - cytology; Hypothalamus - growth & development; Hypothalamus - metabolism; Insulin; Insulin - metabolism; Medical sciences; Metabolic diseases; Microvascular Angina - metabolism; Microvascular Angina - pathology; Neurons - chemistry; Neurons - ultrastructure; Obesity; Obesity - metabolism; Obesity - pathology; Obesity - physiopathology; Rats; Rats, Wistar; Syndrome X; Weaning; Syndrome X; Hypothalamus; Galanin; Early overnutrition; Insulin; Endocrinopathy; Obesity; Pancreatic hormone; Feeding behavior; Rat; Rodentia; Central nervous system; Cardiovascular disease; Metabolic diseases; Neuropeptide; Postnatal development; Feeding; Vertebrata; Mammalia; Malformation; X Syndrome; Animal; Risk factor; Brain (vertebrata)
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(99)01662-5

Overnutrition during critical developmental periods is suggested to be a risk factor for obesity and associated metabolic disorders in later life. Underlying mechanisms are unknown. Neuropeptides are essentially involved in the central nervous regulation of body weight. For instance, hypothalamic galanin (GAL) is a stimulator of food intake and body weight gain. To investigate long-term consequences of early postnatal overfeeding, the normal litter size of Wistar rats ( n=10; controls) was reduced from day 3 to day 21 of life to only 3 pups per mother (small litters, SL; overnutrition). Throughout life, SL rats displayed hyperphagia ( p<0.01), overweight ( p<0.0001), hyperinsulinemia ( p<0.01), impaired glucose tolerance ( p<0.001), elevated triglycerides ( p<0.001), and an increased systolic blood pressure ( p<0.05). In adulthood, an increase of GAL-neurons in the arcuate hypothalamic nucleus (ARC) was found ( p<0.001), positively correlated to body weight ( p<0.001). A second experiment revealed hyperinsulinemia ( p<0.001) and increased hypothalamic insulin levels ( p<0.05) in SL rats during early postnatal life. Already on day 21 of life, i.e., at the end of the critical hypothalamic differentiation period, in SL rats the number of GAL-neurons was increased in the ARC ( p<0.001), showing a positive correlation to body weight and insulin ( p<0.05). In conclusion, neonatally acquired persisting malformation of hypothalamic galaninergic neurons, induced by early overfeeding and hyperinsulinism, might promote the development of overweight and syndrome X-like alterations during life.