Brown adipose tissue characteristics of epicardial fat and its relationship with growth during ageing in early life

We have recently demonstrated, in human adults, that epicardial adipose tissue (EAT) is a depot which demonstrates characteristics of beige fat (Sacks et al (2013) JCEM 98, E1448–55). Its close proximity and intimate vascular connections to the myocardium and the coronary vasculature potentially exploits the efficacy of brown adipocytes in clearing lipoproteins and glucose from the circulation. We now report that biopsies taken from 46 paediatric cases undergoing cardiac surgery for congenital heart disease are characterised as being brown. These samples were analysed both histologically and using Affimetrix (Human Genome U133A plus 2) microarrays on extracted RNA. All EAT taken from newborns, infants and children expresses the brown adipocyte specific uncoupling protein (UCP)1. Histologically, all newborn exhibited EAT that was composed of small multilocular, UCP1 positive adipocytes ( Fig A,B). EAT in infants and children, was however, predominantly comprised of large, unilocular, UCP1 negative cells ( Fig C,D), although around a quarter of those over 1 month of age had islands of multilocular, UCP1 positive adipocytes interspersed between white adipocytes ( Fig E,F). Using a complementary systems biology approach to construct gene networks, by dividing EAT genes into pathways according to their expression and then segregating them into functional groups, we identified biologically important genes within these pathways. We found that EAT of newborns was characterised by clusters of genes implicated in the control of thermogenesis, together with networks of genes with high degrees of connectivity reflecting control of cell differentiation and mitochondrial function. We also found evidence of an elevated need for the utilisation and transport of cellular supplies usually required for the activation of thermogenesis, together with the neutralisation of metabolic by‐products (e.g. oxidised fatty acids), with increased expression of genes associated with cellular retention of vesicles. Furthermore, gene to gene interactions shifted towards lipogenesis through infancy, although distinct thermogenic pathways were also present in infants and children. In addition we found that there was a strong negative association between the expression of UCP1 and related genes with the infant or child's rate of growth i.e. weight for age/height Z score (e.g. R2 −0.54 P<0.003). In conclusion, the apparent inhibition of cell thermogenesis with apparent growth reduction and thus nutritional deficiency is indicative of a protective process, that could ultimately determine the later function and environmental responsiveness of EAT. Consequently, less energy would be expended for temperature regulation by EAT with age, as there is a shift towards pathways that conserve energy for growth and maturation. Support or Funding Information Cardiometabolic Disease Research Foundation, Angeles CA USARelative uncoupling protein (UCP)1 abundance in epicardial adipose tissue with age. Representative immunohistochemical detection of UCP1 in a,b) a 6 day old newborn; c,d) an 18 month old infant and e,f) a 3 year old child: antibody negative (a,c,e) and antibody positive (b,d,f) showing the presence of small multilocular adipocytes (indicated by arrows on e,f) stained positive for UCP1 demonstrating that these are brown adipocytes and the depot is brown fat.