Sex differences in the cannabinoid regulation of energy homeostasis.
Sex differences in the cannabinoid regulation of energy homeostasis.
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DOI：
10.1016/j.psyneuen.2009.04.007
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发表时间：
2009-12-01
影响因子：
3.7
通讯作者：
Wagner, Edward J
中科院分区：
文献类型：
--
作者：
Farhang, Borzoo;Diaz, Shanna;Wagner, Edward J
这篇综述强调了迄今为止在表征大麻素调节能量稳态的行为和细胞机制方面取得的进展。我们对性腺切除的豚鼠和性腺完整的转基因CB 1受体敲除小鼠的摄食行为进行了显微结构分析，以确定大麻素如何影响食物摄入和膳食模式的昼夜节律。我们还将数据记录器植入腹腔，将大麻素的食欲调节特性与核心体温的变化相关联。然后，我们通过弓状核（ARC）神经元的全细胞膜片钳电生理记录，将对摄食行为和温度调节的影响与下丘脑摄食回路中的突触变化相结合，以获得对大麻素调节能量稳态的更全面的观点。我们观察到大麻素对食物摄入量和核心体温的影响存在显著的性别差异-雄性豚鼠对CB 1受体激动剂和拮抗剂分别产生的摄食量过多和摄食量不足以及体温过低和体温过高表现出相对更高的敏感性。此外，雄性而非雌性CB 1受体敲除小鼠显示相对于其野生型同窝对照的夜间食物摄入和平均每日体重减少。在CB 1受体介导的摄食过多的差异是由性别差异，大麻素的细胞效应在oxidogenic，豚鼠前阿黑皮素（POMC）突触。在突触后，大麻素增强雌性豚鼠POMC神经元的A型K+电流（I（A）），而在雄性中观察到向内整流K+电流的激活。在突触前，虽然大麻素抑制在男性和女性的POMC神经元上的GABA能输入到相似的程度，男性比女性更难控制大麻素诱导的收敛GABA能输入的抑制。这些数据揭示了广泛的性别差异，大麻素调节能量稳态，POMC神经元的兴奋性的变化是一致的。
This review highlights the progress made thus far in characterizing the behavioral and cellular mechanisms through which cannabinoids regulate energy homeostasis. We performed microstructural analysis of feeding behavior in gonadectomized guinea pigs and gonadally intact, transgenic CB1 receptor knockout mice to determine how cannabinoids affect circadian rhythms in food intake and meal pattern. We also implanted data loggers into the abdominal cavity to correlate the appetite-modulating properties of cannabinoids with changes in core body temperature. We then coupled the effects on feeding behavior and temperature regulation with synaptic changes in the hypothalamic feeding circuitry via whole-cell patch clamp electrophysiological recording from neurons in the arcuate nucleus (ARC), in order to gain a more global perspective on the cannabinoid modulation of energy homeostasis. We observed marked sex differences in cannabinoid effects on food intake and core body temperature--with male guinea pigs exhibiting a comparatively greater sensitivity to the hyperphagia and hypophagia, as well as the hypothermia and hyperthermia, produced by CB1 receptor agonists and antagonists, respectively. In addition, male but not female CB1 receptor knockout mice show a diminished nocturnal food intake and average daily body weight relative to their wildtype littermate controls. The disparity in the CB1 receptor-mediated hyperphagia is paralleled by sex differences in the cellular effects of cannabinoids at anorexigenic, guinea pig proopiomelanocortin (POMC) synapses. Postsynaptically, cannabinoids potentiate an A-type K+ current (I(A)) in POMC neurons from female guinea pigs, whereas in males the activation of an inwardly rectifying K+ current is observed. Presynaptically, while cannabinoids inhibit glutamatergic input onto POMC neurons in males and females to similar degrees, males are more refractory to the cannabinoid-induced inhibition of convergent GABAergic input than females. These data reveal pervasive sex differences in the cannabinoid regulation of energy homeostasis that are consistent with changes in the excitability of POMC neurons.