Presented at the Neonatal Society 2015 Summer Meeting.
Ojha S1, Symonds M, Lotto A, Budge H
Academic Child Health, School of Medicine, University of Nottingham, Nottingham, UK
Background: Suboptimal nutrition in early life induces metabolic adaptations that may confer short-term survival advantages but are detrimental in later life (1). Brown adipose tissue (BAT) has a unique role in energy homeostasis and a potential role in lipid and glucose metabolism. BAT activation is a mechanism against excess weight gain and can increase clearance of lipids and glucose. Epicardial fat is anatomically and clinically related to cardiac function and modulates the evolution of cardiovascular pathologies. We have previously shown that BAT is present in adipose tissue depots around the heart in fetal (2) and newborn (3) sheep, and in adult humans (4), and that BAT development in early life is affected by suboptimal maternal nutrition during pregnancy, at least in sheep (2,3). We hypothesised that epicardial fat is a BAT depot in newborn infants and children and that suboptimal nutrition in early life affects adiposity and BAT development in humans.
Methods: With appropriate ethical approvals and informed parental consent, clinical data and epicardial adipose tissue samples were collected from 63 children (0-18y) undergoing cardiac surgery. Anthropometric assessment was performed using the Emergency Nutritional Assessment Tool and the World Health Organisation Antro (v3.2.2). Relative abundance of gene expression for uncoupling protein (UCP)1, the unique BAT protein, and other adipose tissue related genes was measured by microarray analysis. Histology and immunohistochemical analyses of adipose tissue sections were performed to confirm the presence of BAT and UCP1 in this depot.
Results: UCP1 gene was highly expressed in epicardial fat of newborn infants. High levels of UCP1 gene expression was also present in older children and did not change significantly with age. Among children ≤2y of age, UCP1 gene expression did not correlate with age but was higher in children of Caucasian origin when compared to children of Asian origin (UCP1 mRNA: Caucasian, 10.02 ± 0.48; Asian/mixed, 7.61 ± 0.99 relative signal intensity in arbitrary units (mean ± SEM) p = 0.02). Gene expression of UCP1 and leptin (a marker for white adipose tissue) correlated with weight for age z-scores (WAZ) independent of age and gender of the participants (UCP1: R2=0.09; p<0.05; leptin: R2=0.12; p<0.05). Children with high UCP1 gene expression also had increased expression of other BAT related genes such as DIO2, PPARα and type 3 beta adrenergic receptor but had decreased expression of glucocorticoid receptor gene. Presence of BAT the epicardial fat depot was confirmed by demonstration of small, multilocular adipocytes that stained positive for UCP1. BAT was demonstrable in all newborn infants and in 23% of older children and adolescents.
Conclusion: Epicardial fat from newborn infants, children and adolescents contains UCP1 confirming that it is a BAT depot in humans. UCP1 gene expression in early years of life in humans is downregulated with poor nutrition. In view of the potential role of BAT in regulation of lipid and glucose metabolism, this may have therapeutic implications for prevention and treatment of cardiovascular complications of obesity.
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1. Ojha, S. et al. (2013), Early Hum Deve, 89:909-13.
2. Ojha, S. et al. (2014), Reprod Fertil Dev.
3. Ojha, S. et al. (2013), Pediatr Res, 74:246-251.
4. Sacks, HS, et al. (2013), J Clin Endocrinol Metab, 98:E1448-55.