hypothalamic neuroendocrine circuitry is programmed by maternal obesity interaction with postnatal nutritional environment下丘脑神经内分泌电路程序由母亲的肥胖与产后营养环境的交互.pdfVIP

Hypothalamic Neuroendocrine Circuitry is Programmed by Maternal Obesity: Interaction with Postnatal Nutritional Environment 1,2 3 1 Hui Chen , David Simar , Margaret J. Morris * 1 Department of Pharmacology, School of Medical Sciences, University of New South Wales, New South Wales, Australia, 2 Department of Medical and Molecular Bioscience, Faculty of Science, University of Technology, Sydney, Australia, 3 Health and Exercise Science, School of Medical Sciences, University of New South Wales, New South Wales, Australia Abstract 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. Research Design and 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