Presented at the Neonatal Society 2011 Autumn Meeting.
Ojha S, Pope M, Symonds ME, Budge H
Early Life Nutrition Research Unit, Academic Child Health, University Hospital, Nottingham,
NG7 2UH
Background: Adipose tissue is now recognised as a highly vascular and metabolically active organ. Different adipose tissue depots have been associated with variable risks of the metabolic consequences of obesity (1). Pericardial adipose tissue (PcAT) is a depot of intra-thoracic fat. The prevalence of cardiovascular disease is associated with increased PcAT after adjustment for age, sex, body mass index, waist circumference (2). In this study, we aim to study the early development of PcAT to determine how key markers of brown and white adipocyte development change from birth to early infancy.
Methods: Samples were obtained from the offspring of twin-bearing sheep. PcAT was sampled immediately after humane euthanasia from one twin at 6 hours and the other twin from each twin pair at 30 days of age. All procedures were conducted with Home Office Approval under UK legislation. Offspring of mothers fed 100% of total metabolisable energy requirements throughout pregnancy (C) whilst nutrient restricted mothers (NR) were fed 60% of this amount In late gestation. Gene expression for key markers of brown adipose tissue was determined using qPCR.
Results: Absolute and relative PcAT weights increased significantly between 0 and 30 days postnatal age in offspring of both C (C, 0 days: 1.00 ± 0.12g/Kg; C, 30 days: 1.42 ± 0.11g/Kg Δ2ct: 18S (p<0.05)) and NR (NR, 0 days: 0.91 ± 0.30g/Kg; NR, 30 days: 1.31 ± 0.06 (p<0.05)) mothers. Uncoupling protein 1 (UCP1) gene expression was significantly reduced at 30 days postnatal age as compared to 0 days postnatal age in the offspring of both C (C, 0 days: 1.00 ± 0.55; C, 30 days: 0.01 ± 0.00 (p<0.005)) and NR (C, 0 days: 0.94 ± 0.35; C, 30 days: 0.01 ± 0.00 (p<0.005) mothers. Other brown adipose tissue (BAT) markers such as TGM2 (p<0.005) and KCNK3 (p<0.05) also showed a similar decline. Expression of TGM2 and KCNK3 was reduced in offspring of NR mothers compared to offspring of C mothers on the first postnatal day but this difference disappeared by 30 days postnatal age. Prolactin receptor (PRLR) expression also decreased in the first month after birth (C, 0 days: 1.00 ± 0.21; C, 30 days: 0.46 ± 0.01 (p<0.005)); NR, 0 days: 0.76 ± 0.14; NR, 30 days: 0.13 ± 0.05 (p<0.005) in both groups but the expression of BMP4 and ADRP was unchanged.
Conclusion: The presence of BAT markers in PcAT at birth provides evidence that, like in the perirenal depot, brown adipocytes are present at birth. These markers decline thereafter, in a pattern similar to other adipose tissue depots (3,7).
Although UCP1 expression at birth was not affected by maternal nutrient restriction, expression of some BAT specific genes including TGM2 and KCNK3 was reduced. TGM2 plays a role in cell growth and survival through the anti-apoptosis pathway (4) whilst KCNK3 codes for voltage-insensitive background potassium channel protein which may also enhance cell survival (5). Both these genes are also highly expressed in BAT in humans (6). Their reduced expression with maternal nutrient restriction suggests that, although the amount of BAT is not affected, it may influence the survival of BAT cells. PRLRs are highly expressed in fetal BAT and their peak coincides with the increase in UCP1 in preparation for birth (7). These latest results also illustrate that maternal nutrient restriction can also affect the course of pericardial adipose tissue development.
Corresponding author: helen.budge@nottingham.ac.uk
References
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