Adipose tissue is a central node for the dynamic regulation of systemic metabolism and energy expenditure. Little is known about adipogenesis in the newborn which is the critical window of adipose tissue development. Emerging data suggest that immune cells, particularly innate immune cells, play an important role in de novo beige adipogenesis and beige fat thermogenesis in mature rodents. In previous studies we showed that administration of low levels of IL-4 in the first week of life to rat pups results in decreased adiposity and improved glucose tolerance in adulthood, suggesting that beige adipogenesis may be enhanced by neonatal IL-4 administration. Developing animals produce higher levels of IL-4 compared to mature animals and use a distinct pre-adipocyte compartment for adipogenesis. In this study, we analyze the effects of IL-4 on adipogenesis in the developing rat. We demonstrate that a short and transient IL-4 exposure in the neonate during postnatal days 1-6 induces acute beige adipogenesis in the inguinal white adipose tissue (iWAT) that is associated with the upregulation of Ucp1 (n=6). Concurrently, adipocyte maturation is decreased with Adipoq downregulated (n=6). Pre-adipocytes from 10 week old mature rats that had been treated with IL-4 as neonates were differentiated in vitro and also show a decrease in Adipoq compared to controls (n=6). These data demonstrate that neonatal IL-4 induces a long term decrease in the maturation potential of pre-adipocytes. Interestingly, these adult differentiated pre-adipocytes show no change in Ucp1 expression after neonatal IL-4 exposure compared to control (n=6). Thus, neonatal IL-4 induces only acute beige adipogenesis, but impairs adipocyte maturation long term. Phenotypically, neonatal IL-4 resulted in decreased iWAT (n=7) and decreased fasting blood glucose in 10 week old animals (n=6) compared to control. Our studies show that the neonatal period is critical for adipocyte development and may influence the later onset of obesity.


T. Ying: None. P. Seale: None. R.A. Simmons: None.


National Institutes of Health (DK114054)

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