Department of Neurobiology of Rhythms, Institute of Cellular and Integrative Neurosciences, Centre National de la Recherche Scientifique, UPR3212 University of Strasbourg, Strasbourg, France.
J Neuroendocrinol. 2011 Jan;23(1):28-38. doi: 10.1111/j.1365-2826.2010.02072.x.
The hormone leptin controls food intake and body weight through its receptor in the hypothalamus, and may modulate physiological functions such as reproduction, sleep or circadian timing. In the present study, the effects of leptin on the resetting of the circadian clock, the hypothalamic suprachiasmatic nucleus (SCN) and on the activity of the hypocretinergic system were examined in vivo, with comparative analysis between male and female mice. A single leptin injection (5 mg/kg) at both the onset and offset of the activity period did not alter locomotion of mice housed under a 12 : 12 h light/dark cycle and did not shift the circadian behavioral rhythm of mice housed in constant darkness. By contrast, leptin potentiated the phase-shifting effect of a 30-min light-pulse on behavioural rhythms during the late subjective night, although only in females. This was accompanied by a higher induction of the clock genes Per1 and Per2 in the SCN. A 2-week chronic exposure to a physiological dose of leptin (100 μg/kg per day) decreased locomotor activity, expression of hypocretin receptor 1 and 2, as well as the number of hypocretin-immunoreactive neurones only in female mice, whereas the number of c-fos-positive hypocretinergic neurones was reduced in both genders. These results highlight a dimorphic effect of leptin on the hypocretinergic system and on the response of the circadian clock to light. Leptin may thus modulate the sleep/wake cycle and circadian system beside its well-established action on food intake and regulation of body weight.
瘦素通过其在下丘脑的受体控制食物摄入和体重，并且可能调节生理功能，如生殖、睡眠或昼夜节律。在本研究中，研究了瘦素对生物钟的重置、下丘脑视交叉上核（SCN）以及下丘脑泌素能系统活性的影响，同时对雄性和雌性小鼠进行了比较分析。在活动期开始和结束时，单次注射瘦素（5mg/kg）不会改变在 12:12 小时光照/黑暗周期下饲养的小鼠的运动，也不会改变在持续黑暗中饲养的小鼠的昼夜节律行为节律。相比之下，瘦素增强了 30 分钟光脉冲对夜间后期行为节律的相位移动作用，但仅在雌性小鼠中。这伴随着 SCN 中时钟基因 Per1 和 Per2 的更高诱导。为期两周的生理剂量瘦素（100μg/kg/天）慢性暴露会降低雌性小鼠的运动活性、下丘脑泌素受体 1 和 2 的表达以及下丘脑泌素免疫反应性神经元的数量，而两性的 c-fos 阳性下丘脑泌素能神经元数量均减少。这些结果突出了瘦素对下丘脑泌素能系统和生物钟对光的反应的性别二态效应。因此，瘦素可能除了对食物摄入和体重调节的既定作用外，还调节睡眠/唤醒周期和昼夜节律系统。
