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Submitted on March 20, 2007
Accepted on May 16, 2007
Division of Neuroscience, Oregon National Primate Research Center, Department of Physiology and Pharmacology, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006
* To whom correspondence should be addressed. E-mail: grovek{at}ohsu.edu.
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 small litter (SL, 3 pups/litter) were compared with those raised in a normal litter size (NL, 8 pups/litter). BAT from young adult NL and SL rats, maintained at either ambient or cold condition, 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 at cold condition. Finally, the expression of sympathetic
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.
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