Endocrine Abstracts (2015) 38 P230 | DOI: 10.1530/endoabs.38.P230

Maternal overnutrition programs hypothalamic neuropeptides and metabolic syndrome in offspring

Thanuja Gali Ramamoorthy1, Tiffany-Jayne Allen1, Alison Davies1, Erika Harno1, Charlotte Sefton1, Jonathan Wray1, Christopher Murgatroyd2 & Anne White1

1The University of Manchester, Manchester, UK; 2Manchester Metropolitan University, Manchester, UK.

Background and objective: The prevalence of obesity is increasing worldwide and it is known that intra-uterine experience can program metabolic disorders. The hypothalamic appetite regulatory system is a key target of developmental programming by maternal nutrition. Therefore, the aim of this study was to investigate the effects of maternal overnutrition on the expression of hypothalamic genes controlling energy homeostasis.

Research design: Eight week old female Sprague-Dawley rats were fed high fat diet (HFD) or low fat diet (LFD) for 6 weeks before mating, throughout gestation and lactation. At postnatal day 21, hypothalami were collected from half of the offspring and the remaining were weaned onto LFD for 5 weeks, after which they were divided into LFD or HFD fed for 12 weeks.

Results and conclusion: Offspring from HFD fed dams were 32% heavier at birth and gained more weight with increased adiposity compared to those from LFD fed dams, independent of post-weaning diet. Maternal HFD also led to glucose intolerance in offspring at 8 weeks of age. Maternal diet interacted with offspring HFD to cause hyperphagia, increased body weight and epididymal and subcutaneous fat mass. At postnatal day 21, offspring of HFD fed dams had reduced mRNA expression of hypothalamic NPY (approximately twofold), AgRP (approximately twofold) and increased NPY-1 receptor (1.3 fold) but no change in the levels of POMC. The differential expression of AgRP (approximately twofold) and NPY1R (1.6 fold) persisted into adulthood with an increase in POMC expression (1.4 fold) in the offspring fed HFD. However, no change in the mRNA levels of MC4R and orexigenic peptides galanin, enkephalin and dynorphin were observed. These results suggest that maternal overnutrition alters central appetite neuroendocrine circuitry and exerts a detrimental effect on the offsprings’ metabolic homeostasis. Postnatal overnutrition has additive effects with maternal programming to increase metabolic disorders.

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