Excess
weight gain during the early postnatal period increases the risk of persistent
obesity into adulthood and impacts on the subsequent risk for metabolic and
cardiovascular diseases. The current study investigated the long-term effect of early excess
weight gain, through reduced nursing litter size, on
body weight regulation and its relation to brown adipose tissue (BAT) thermogenesis. Animals raised in a small litter (SL, three pups per litter) were compared with those raised in a normal litter size (NL, eight pups per litter). BAT from young adult NL and SL rats, maintained under either ambient or cold conditions, were used for gene expression, morphological, and functional analysis. Compared with NL, SL rats showed excess
weight gain, and adult SL animals had a reduced thermogenic capacity as displayed by lower levels of
uncoupling protein 1 (UCP1). When exposed to cold, BAT from SL rats was less active and demonstrated reduced responsiveness to cold. Furthermore, reduction in transcript abundance of several
lipid lipases and transcriptional regulators was observed in SL rats either at ambient temperature or under cold conditions. Finally, the expression of sympathetic beta 3-adrenergic receptor and the response to the sympathetic receptor agonist
isoproterenol were decreased in SL rats. Overall, these observations provide the first evidence that postnatal excess
weight gain results in abnormalities in BAT thermogenesis and sympathetic outflow, which likely increases susceptibility to
obesity in adulthood.