Denis R G P, Bing C, Naderali E K, Vernon R G, Williams G
Diabetes and Endocrinology Research Group, Department of Medicine, The University of Liverpool, Liverpool, UK.
J Endocrinol. 2003 Aug;178(2):225-32. doi: 10.1677/joe.0.1780225.
We investigated the effects of lactation on diurnal changes in serum leptin and hypothalamic expression of the leptin receptor isoforms, Ob-Ra, -Rb, -Rc, -Re and -Rf in rats. In non-lactating rats, serum leptin concentration was increased at night while hypothalamic mRNA levels of Ob-Rb, -Rc and -Re decreased; by contrast, expression of Ob-Ra and Ob-Rf was unchanged at night. There were significant negative correlations between serum leptin and mRNA expression of Ob-Rb (P<0.001) and Ob-Re (P<0.05), which were independent of time of day. In lactating rats, the nocturnal rise in serum leptin was attenuated. Daytime hypothalamic Ob-Rb mRNA levels were significantly lower than in non-lactating controls, and the normal nocturnal decreases in expression of Ob-Rb, -Rc and -Re were lost. The relationship between serum leptin and Ob-Re expression was not changed by lactation. Lactation had no effect on the expression of Ob-Ra mRNA in the hypothalamus. Decreased daytime Ob-Rb expression could lead to reduced hypothalamic sensitivity to leptin, and thus contribute to increased daytime appetite in lactating rats. Moreover, maintaining high levels of Ob-Re expression could, by increasing hypothalamic leptin-binding protein concentration and reducing local leptin bioavailability, further accentuate hyperphagia. Thus, selective changes in expression of specific isoforms of the leptin receptor may contribute to the hyperphagia of lactation in rats.
我们研究了哺乳对大鼠血清瘦素昼夜变化以及下丘脑瘦素受体亚型Ob-Ra、-Rb、-Rc、-Re和-Rf表达的影响。在非哺乳大鼠中，夜间血清瘦素浓度升高，而Ob-Rb、-Rc和-Re的下丘脑mRNA水平下降；相比之下，Ob-Ra和Ob-Rf的表达在夜间没有变化。血清瘦素与Ob-Rb（P<0.001）和Ob-Re（P<0.05）的mRNA表达之间存在显著负相关，且与一天中的时间无关。在哺乳大鼠中，血清瘦素的夜间升高减弱。白天下丘脑Ob-Rb mRNA水平显著低于非哺乳对照组，Ob-Rb、-Rc和-Re正常的夜间表达下降消失。哺乳对血清瘦素与Ob-Re表达之间的关系没有影响。哺乳对下丘脑Ob-Ra mRNA的表达没有影响。白天Ob-Rb表达降低可能导致下丘脑对瘦素的敏感性降低，从而导致哺乳大鼠白天食欲增加。此外，维持高水平的Ob-Re表达可能通过增加下丘脑瘦素结合蛋白浓度和降低局部瘦素生物利用度，进一步加剧食欲亢进。因此，瘦素受体特定亚型表达的选择性变化可能导致大鼠哺乳期的食欲亢进。
