Appetite regulation and seasonality: implications for obesity
Appetite regulation and seasonality: implications for obesity
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DOI：
10.1079/pns2004367
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发表时间：
2004-08-01
影响因子：
7
通讯作者：
Mercer, JG
中科院分区：
文献类型：
--
作者：
Adam, CL;Mercer, JG
肥胖患者体内的高循环瘦素浓度与其在大脑下丘脑区域的典型厌食作用的明显丧失有关。因此，对瘦素的中枢不敏感可能有助于这种疾病的病因学，对潜在机制的进一步了解将确定预防和/或治疗目标的潜在手段。季节性动物如绵羊和西伯利亚仓鼠（Phodopus sungorus）表现出每年由光周期驱动的食欲和体重周期。长时间（夏季）的食物摄入增加和体重增加与高循环瘦素有关，短时间（冬季）的摄入减少和体重减轻与低循环瘦素有关。关键的是，这些周期与对瘦素敏感性的可逆变化有关。在短时间内观察到高敏感性，而在长时间内观察到相对不敏感，这在通过脑室内插管中央给予瘦素的绵羊和外周给予瘦素的仓鼠中都表现出来。此外，在这些物种中，瘦素的主要下丘脑食欲调节靶点（即神经肽Y、黑素皮质素以及可卡因和安非他明调节的转录途径）对光周期引起的循环瘦素和营养状况变化的反应不同，而不是食物限制引起的这种变化。对季节性动物的研究将有助于解决瘦素敏感性改变的原因，以及这些变化是否反映了进入大脑的运输改变和/或受体或受体后水平的信号传导改变。增加对中枢瘦素敏感性降低的发生和逆转的机制和时间过程的了解，将为肥胖的发生和控制提供新的见解。
High circulating concentrations of leptin in obesity are associated with an apparent loss of its characteristic anorexic action within the hypothalamic region of the brain. Central insensitivity to leptin may therefore contribute to the aetiology of this disease, and an increased understanding of the underlying mechanisms will identify potential means of prevention and/or therapeutic targets. Seasonal animals such as sheep and Siberian hamsters (Phodopus sungorus) exhibit annual photoperiod-driven cycles of appetite and body weight. Increased food intake and weight gain in long days (summer) are associated with high circulating leptin, and decreased intake and weight loss in short days (winter) with low leptin. Critically, these cycles are associated with reversible changes in sensitivity to leptin. High sensitivity is seen in short days and relative insensitivity in long days, demonstrated both in sheep given leptin centrally via intracerebroventricular cannulas and in hamsters given leptin peripherally. In addition, primary hypothalamic appetite-regulating targets for leptin (i.e. neuropeptide Y, melanocortin and cocaine- and amphetamine-regulated transcript pathways) respond differently in these species to changes in circulating leptin and nutritional status induced by photoperiod as opposed to such changes induced by food restriction. Studies of seasonal animals will help to resolve causes of altered sensitivity to leptin and whether these changes reflect altered transport into the brain and/or altered signalling at the receptor or post-receptor level. Increased knowledge of the mechanism(s) and time-course for development and reversal of reduced central leptin sensitivity will provide new insights into the development and control of obesity.