Pouteau E, Turner S, Aprikian O, Hellerstein M, Moser M, Darimont C, Fay L B, Macé K
Nestlé Research Center, Nutrition and Health Department, Vers-Chez-Les-Blanc, Lausanne, Switzerland.
Int J Obes (Lond). 2008 Apr;32(4):648-57. doi: 10.1038/sj.ijo.0803787. Epub 2007 Dec 18.
To evaluate the ontogeny of adipose tissue dynamics in obese and lean Zucker rat pups, from suckling to puberty.
The trial had a two-group parallel design. Sixty-two male Zucker rat pups shared within 15 litters received deuterated water for 5 days, prior killing at different age. Adipose tissues were collected for (2)H-enrichment analyses using mass spectrometry to determine fat cell proliferation and lipid synthesis rates. Rats were assigned to obese and lean rat groups by genotyping.
The time course (from days 13 to 55) of all adipose tissue growth showed that the highest fractional rates of fat cell proliferation, triacylglycerol (TG) synthesis and de novo lipogenesis (DNL) took place during early suckling in all rat pups. The appearance of excessive fat mass growth in the obese rats, as compared with lean rats, was first shown through a significant increase in DNL at the end of suckling (P<0.05). The TG synthesis rate was enhanced (P<0.05) from the end of suckling and early postweaning until day 55 (from 122+/-10 to 498+/-78 in obese pups and from 25+/-6 to 75+/-26 mg new TG per day in lean pups (median+/-s.e.m., P<0.01)). In contrast, only by day 55 did the fractional proliferation rate of fat cells in retroperitoneal and epididymal depots in the obese rats supersede that of the lean rats (P<0.05).
The early suckling period constitutes the most active period for adipose tissue development in normal rats. In the obese Zucker rat model, adipose hypertrophy primarily contributes to the early onset of obesity, while hyperplasia increases after puberty. Early onset of adipose tissue growth may play a determinant role in the development of obesity later in life.
评估肥胖和瘦型 Zucker 大鼠幼崽从哺乳期到青春期脂肪组织动态变化的个体发育情况。
试验采用两组平行设计。将 15 窝内的 62 只雄性 Zucker 大鼠幼崽在不同年龄处死前给予氘代水 5 天。收集脂肪组织进行质谱分析以测定(2)H 富集情况,从而确定脂肪细胞增殖和脂质合成速率。通过基因分型将大鼠分为肥胖组和瘦型组。
所有脂肪组织生长的时间进程(从第 13 天到第 55 天)表明,所有大鼠幼崽在哺乳早期脂肪细胞增殖、三酰甘油(TG)合成和从头脂肪生成(DNL)的分数率最高。与瘦型大鼠相比,肥胖大鼠脂肪量过度增长首先表现为哺乳期末 DNL 显著增加(P<0.05)。从哺乳期末和断奶早期到第 55 天,TG 合成速率增强(P<0.05)(肥胖幼崽从 122±10 增加到 498±78,瘦型幼崽从 25±6 增加到 75±26 毫克新 TG/天(中位数±标准误,P<0.01))。相比之下,直到第 55 天,肥胖大鼠腹膜后和附睾脂肪库中脂肪细胞的分数增殖率才超过瘦型大鼠(P<0.05)。
哺乳早期是正常大鼠脂肪组织发育最活跃的时期。在肥胖 Zucker 大鼠模型中,脂肪肥大主要导致肥胖的早期发生,而增生在青春期后增加。脂肪组织生长的早期发生可能在生命后期肥胖的发展中起决定性作用。