Hypothalamic neuroendocrine circuitry is programmed by maternal obesity: interaction with postnatal nutritional environment.
OBJECTIVE
Early life nutrition is critical for the development of hypothalamic neurons involved in energy homeostasis. We previously showed that intrauterine and early postnatal overnutrition programmed hypothalamic neurons expressing the appetite stimulator neuropeptide Y (NPY) and suppressor proopiomelanocortin (POMC) in offspring at weaning. However, the long-term effects of such programming and its interactions with post-weaning high-fat-diet (HFD) consumption are unclear.


METHODS
Female Sprague Dawley rats were exposed to chow or HFD for 5 weeks before mating, throughout gestation and lactation. On postnatal day 1, litters were adjusted to 3/litter to induce postnatal overnutrition (vs. 12 in control). At postnatal day 20, half of the rats from each maternal group were weaned onto chow or HFD for 15 weeks. Hypothalamic appetite regulators, and fuel (glucose and lipid) metabolic markers were measured.


RESULTS
Offspring from obese dams gained more weight than those from lean dams independent of post-weaning diet. Maternal obesity interacted with post-weaning HFD consumption to cause greater levels of hyperphagia, adiposity, hyperlipidemia, and glucose intolerance in offspring. This was linked to increased hypothalamic NPY signaling and leptin resistance in adult offspring. Litter size reduction had a detrimental impact on insulin and adiponectin, while hypothalamic NPY and POMC mRNA expression were suppressed in the face of normal energy intake and weight gain.


CONCLUSIONS
Maternal obesity, postnatal litter size reduction and post-weaning HFD consumption caused obesity via different neuroendocrine mechanism. There were strong additive effects of maternal obesity and post-weaning HFD consumption to increase the metabolic disorders in offspring.
Chen
Hui
H
Department of Pharmacology, School of Medical Sciences, University of New South Wales, New South Wales, Australia.
Simar
David
D
Morris
Margaret J
MJ
D000818:Animals; D001483:Base Sequence; D015342:DNA Probes; D005260:Female; D007031:Hypothalamus / Q000503:physiopathology*; D008098:Litter Size; D009490:Neurosecretory Systems / Q000503:physiopathology*; D009752:Nutritional Status; D009765:Obesity / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley
D015342:DNA Probes