Schmidt I, Fritz A, Schölch C, Schneider D, Simon E, Plagemann A
Max-Planck-Institut für physiologische und klinische Forschung, W.G. Kerckhoff-Institut, Bad Nauheim, Germany.
Int J Obes Relat Metab Disord. 2001 Aug;25(8):1168-74. doi: 10.1038/sj.ijo.0801669.
To identify the role of hyperleptinaemia in mediating the effects of early postnatal overfeeding in a rat strain known to be prone to manipulations of the early environment which result in predispositions for obesity and associated metabolic and cardiovascular disturbance in later life.
Wistar rats were reared in normal litters (NL, 10--12 pups) or small litters (SL, four pups) from postnatal day 3 and killed for determination of body composition and plasma leptin and insulin concentrations on day 7 or day 21 after having been treated with recombinant leptin (2 x 50 (pmol/g)/day) or saline from day 1.
Rearing in SL doubled the body fat content and plasma leptin levels in comparison to NL pups by 21 days of age. Under leptin-treatment throughout suckling age, NL pups remained leptin responsive, ie the difference in body fat content was progressively reduced relative to the controls. Until 7 days of age, despite the body fat content of untreated SL pups being 2-fold higher and their plasma leptin level 7-fold higher than that of NL pups, leptin treatment caused the same percentage decreases in body fat in SL than in NL pups. But in contrast to NL pups, the SL pups became leptin resistant thereafter. Plasma insulin levels in 7-day-old leptin-treated SL pups were 3-fold higher than in untreated littermates and 5-fold higher than in the NL groups.
Prophylactic leptin treatment does not prevent hyperinsulinaemia and excessive fat deposition in SL pups. On the other hand, selective hyperleptinaemia during suckling age does not trigger leptin resistance and obesity in NL pups. Rather than hyperleptinaemia per se, other factors associated with early postnatal overnutrition, for example, the concurrent hyperinsulinaemia, seem to play a pivotal role for the development of leptin-resistance and life-long obesity risk in SL rats.
在一种已知易于受早期环境操纵影响的大鼠品系中，确定高瘦素血症在介导出生后早期过度喂养的影响方面所起的作用，这种早期环境操纵会导致大鼠在后期生活中易患肥胖症以及相关的代谢和心血管紊乱。
从出生后第3天起，将Wistar大鼠饲养在正常窝（NL，10 - 12只幼崽）或小窝（SL，4只幼崽）中，并在从第1天开始用重组瘦素（2×50（pmol/g）/天）或生理盐水处理后，于第7天或第21天处死，以测定身体组成以及血浆瘦素和胰岛素浓度。
与NL幼崽相比，饲养在SL中的幼崽到21日龄时身体脂肪含量和血浆瘦素水平增加了一倍。在整个哺乳期接受瘦素治疗的情况下，NL幼崽仍对瘦素敏感，即相对于对照组，身体脂肪含量的差异逐渐减小。直到7日龄，尽管未治疗的SL幼崽的身体脂肪含量比NL幼崽高2倍，血浆瘦素水平高7倍，但瘦素治疗使SL幼崽的身体脂肪减少的百分比与NL幼崽相同。但与NL幼崽不同的是，此后SL幼崽变得对瘦素抵抗。在7日龄接受瘦素治疗的SL幼崽中，血浆胰岛素水平比未治疗的同窝幼崽高3倍，比NL组高5倍。
预防性瘦素治疗不能预防SL幼崽的高胰岛素血症和过多的脂肪沉积。另一方面，哺乳期的选择性高瘦素血症不会引发NL幼崽的瘦素抵抗和肥胖。与出生后早期营养过剩相关的其他因素，例如同时存在的高胰岛素血症，似乎比高瘦素血症本身在SL大鼠瘦素抵抗和终生肥胖风险的发展中起关键作用。
