Otukonyong Effiong E, Dube Michael G, Torto Rita, Kalra Pushpa S, Kalra Satya P
Department of Neuroscience, McKnight Brain Institute, University of Florida, College of Medicine, P.O. Box 100244, Gainesville, FL 32610-0244, USA.
Peptides. 2005 Dec;26(12):2559-66. doi: 10.1016/j.peptides.2005.04.015. Epub 2005 Jun 4.
We tested the hypothesis that leptin acts centrally to differentially modulate the ultradian communication of leptin, insulin and ghrelin with the hypothalamus. The ultradian fluctuation of these hormones in plasma after central leptin gene therapy was analyzed. Increased leptin transgene expression in the hypothalamus significantly decreased energy intake and body weight concomitant with severe hypoleptinemia and hypoinsulinemia resulting from drastically suppressed peak heights with unchanged frequency discharge of these hormones. Ghrelin secretion was, however, increased solely due to increased pulse amplitude. In pair-fed control rats leptin and ghrelin secretion was unchanged. In conclusion, independent of restraint on caloric intake and weight, leptin acting centrally modulates only the pulse amplitude of ultradian rhythmicity of the three afferent signals involved in the hypothalamic integration of energy balance. Since rhythmic discharge patterns dictate target response of hormones, these findings reveal a novel hypothalamic action of leptin in the pathophysiology of the obesity-dependent metabolic syndrome.
瘦素在中枢发挥作用，以差异性地调节瘦素、胰岛素和胃饥饿素与下丘脑之间的超日节律通讯。分析了中枢性瘦素基因治疗后这些激素在血浆中的超日波动情况。下丘脑内瘦素转基因表达增加，显著降低了能量摄入和体重，同时伴随着严重的低瘦素血症和低胰岛素血症，这是由于这些激素的峰值高度大幅降低而频率放电未变所致。然而，胃饥饿素分泌仅因脉冲幅度增加而升高。在配对喂养的对照大鼠中，瘦素和胃饥饿素分泌未变。总之，不考虑热量摄入和体重的限制，中枢作用的瘦素仅调节参与下丘脑能量平衡整合的三种传入信号超日节律的脉冲幅度。由于节律性放电模式决定激素的靶反应，这些发现揭示了瘦素在肥胖相关代谢综合征病理生理学中的一种新的下丘脑作用。
