Xiao Xiao Qiu, Williams Sarah M, Grayson Bernadette E, Glavas Maria M, Cowley Michael A, Smith M Susan, Grove Kevin L
Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA.
Endocrinology. 2007 Sep;148(9):4150-9. doi: 10.1210/en.2007-0373. Epub 2007 May 24.
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.
出生后早期体重过度增加会增加成年后持续肥胖的风险，并影响随后患代谢性疾病和心血管疾病的风险。本研究通过减少每窝哺乳幼崽数量，调查了早期体重过度增加对体重调节的长期影响及其与棕色脂肪组织（BAT）产热的关系。将饲养在小窝（SL，每窝三只幼崽）中的动物与饲养在正常窝大小（NL，每窝八只幼崽）中的动物进行比较。将成年早期NL和SL大鼠在环境温度或寒冷条件下饲养的BAT用于基因表达、形态学和功能分析。与NL相比，SL大鼠体重过度增加，成年SL动物的产热能力降低，表现为解偶联蛋白1（UCP1）水平较低。暴露于寒冷环境时，SL大鼠的BAT活性较低，对寒冷的反应性降低。此外，在环境温度或寒冷条件下，SL大鼠的几种脂质脂肪酶和转录调节因子的转录丰度均降低。最后，SL大鼠交感β3-肾上腺素能受体的表达及对交感受体激动剂异丙肾上腺素的反应均降低。总体而言，这些观察结果首次证明，出生后体重过度增加会导致BAT产热和交感神经输出异常，这可能会增加成年后患肥胖症的易感性。
