Selective stimulatory actions of corticotropin-releasing factor ligands on correlates of energy balance.
Selective stimulatory actions of corticotropin-releasing factor ligands on correlates of energy balance.
复制标题
促肾上腺皮质激素释放因子配体对能量平衡相关因素的选择性刺激作用。
DOI：
10.1016/s0031-9384(01)00421-8
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发表时间：
2001
影响因子：
2.9
通讯作者：
DeSouza,E
中科院分区：
文献类型：
--
作者：
Heinrichs,SC;Joppa,M;Lapsansky,J;Jeske,K;Nelson,R;DeSouza,E
急性给予促肾上腺皮质激素释放因子(CRF)会导致厌食症和拟交感神经反应，这表明在慢性能量平衡模型中是有效的。本研究在瘦削和遗传性肥胖的Zucker大鼠上采用广谱能量平衡指数，以全面表征CRF和CRF结合蛋白(CRF-BP)配体抑制剂CRF(6-33)的药理作用，CRF被认为可以将CRF从CRF-BP中释放出来。急性给予CRF(6-33)可使Zucker肥胖大鼠下丘脑腹内侧核(VMH)CRF2受体密度增加10%，降低10%。根据瘦大鼠和肥胖大鼠棕色脂肪组织中质子电导的测量，单次注射CRF(6-33)可使非颤抖产热增加25%-30%。长期输注CRF(6-33)可抑制体重增加和核心体温升高，而与基因无关，同时在不改变心率或血压的情况下增加肥胖大鼠的运动活动。综上所述，这些结果证明了CRF-BP配体抑制剂对增加能量消耗的一组选定的生理和行为指标的长期影响。
Acute administration of corticotropin-releasing factor (CRF) results in anorexic and sympathomimetic effects that suggest efficacy in chronic models of energy balance. The present studies employed a broad spectrum energy balance indices in lean and genetically obese Zucker rats in order to fully characterize the pharmacological efficacy of CRF and a CRF binding protein (CRF-BP) ligand inhibitor, CRF(6–33), which is thought to liberate CRF from CRF-BP. Acute administration of CRF(6–33) significantly increased CRF2receptor density by 10% within the ventromedial hypothalamic (VMH) nucleus of Zucker lean rats and decreased density by 10% in Zucker obese rats. A single infusion of CRF(6–33) increased nonshivering thermogenesis by 25–30% as measured by proton conductance in brown adipose tissue of both lean and obese rats. Chronic CRF(6–33) infusion suppressed body weight gain and elevated core temperature irrespective of genotype while increasing motor activity in obese rats without altering heart rate or blood pressure. Taken together, these results document strain-dependent, long-term effects of a CRF-BP ligand inhibitor on a select subset of physiological and behavioral measures of increased energy expenditure.