Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA294

Poster Communications

Implications of maternal obesity on offspring orexigenic neurons development

J. D. Faria1,2, L. Velloso1

1. Obesity and Comorbidities Research Center, State University of Campinas, Cambridge, Cambridgeshire, United Kingdom. 2. Institute of Metabolic Science, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom.


A set of evidences supports the hypothesis that adverse in utero and early postnatal environments have a significant influence on risk of a myriad of prevalent metabolic diseases.So far, a small number of studies have addressed the role of maternal obesity on the hypothalamic structure/activity of the offspring both short and long terms. The hypothalamus responds to nutrients and hormones as well as integrates the resulting signals in order to balance caloric intake and energy expenditure, which affects whole body energy homeostasis. This study aimed to investigate if maternal obesity could impact on the development of hypothalamic neurons, generating long term abnormalities, and to elucidate potential underlying mechanisms. Here, we used a mouse model of maternal diet-induced obesity. Female C57Bl/6J mice were fed either a control (n=9) or a high fat (n=6) diet from three weeks prior to mating and during pregnancy and lactation. Male offspring born from control (n=6 for i and ii) and from obese dams (n=6 for i and ii) were evaluated at different time points: i, immediately after weaning; and ii, at 8 weeks of age (both litters weaned onto a balanced Chow diet). Obese dams presented increased body weight during pregnancy (Obese: 26.53±1.21 vs 22.5456±0.51, p<0.01) as well as in white (normalized by BW, Obese: 1.45±0.24 vs 0.47±0.02, p<0.01) and brown (normalized by BW, Obese: 0.41±0.03 vs 0.31±0.006, p<0.05) adipose tissue in the end of lactation. Additionally, obese dams presented hyperglycemia (mg/dL, Obese: 153.83±4.21 vs 128.11±8.11, p<0.01) and hyperinsulinemia (ng/mL, Obese: 1.47±0.08 vs 0.87±0.12, p<0.01) at weaning. Male offspring born from obese dams presented decreased body weight at birth (g, Obese offs: 1.185±0.03 vs 1.399±0.04, p<0.01). Immunostaining showed that male offspring from obese dams presented increased astrocyte population (qualitative data) in the arcuate nucleus at weaning. In parallel, 8 weeks siblings born from obese dams presented increased gene expression of Tnf-alpha (p<0.01), Interleukin-6 (p<0.05) and the orexigenic neurons, NPY (p<0.05) and AgRP (p<0.05), in hypothalamus. All values are presented as mean ± S.E.M., compared by Student's t-test. The set of results revealed an impaired development of hypothalamic neural circuits modulated by maternal obesity. Our findings suggest that adult offspring from obese dams presented increased levels of important orexigenic and pro-inflammatory components in hypothalamus. Apparently, such outcomes are preceded by an increase in astrocyte population, which control inflammation and neuronal stress, at very premature stage for these animals. As hypothalamus provides many physiological roles involved in feeding and metabolism, the enhanced stress response short term may be favouring the upregulation of NPY and AgRP neurons population long term.

Where applicable, experiments conform with Society ethical requirements