Morrison C D, Wood R, McFadin E L, Whitley N C, Keisler D H
Department of Animal Sciences, University of Missouri-Columbia, 160 Animal Science Research Center, MO 65211, USA.
Domest Anim Endocrinol. 2002 Apr;22(2):103-12. doi: 10.1016/s0739-7240(01)00129-1.
In sheep, serum concentrations of leptin change congruently with increases or decreases in nutritional status, while intracerebroventricular infusions of leptin dramatically suppress feed intake in well-fed lambs, and may also increase growth hormone (GH), and/or luteinizing hormone (LH) in undernourished lambs. The objective of the present study was to determine the effects of peripherally delivered ovine leptin, via intravenous infusions, on feed intake and serum concentrations of GH, LH, insulin, IGF-1, cortisol, and thyroxine. Twelve ewe lambs weighing 29.4 +/- 0.7 kg were infused intravenously with a linearly increasing dose of leptin or saline (n = 6 per group) for 10 days, reaching a maximum dose delivered of 0.5mg/h on day 10. Feed intake was assessed twice daily, and blood samples were collected every 10 min for 6 h on days 0, 2, 5, 8, and 10. Serum concentrations of leptin increased in leptin-treated lambs by day 2 (P = 0.05), and continued to increase to concentrations 9-fold greater than saline-infused lambs by day 10 (P < 0.001). Despite the substantial increase in serum leptin, feed intake did not differ between leptin and saline-infused lambs except on day 3.5 (P = 0.01). Furthermore, intravenous infusions of leptin did not significantly influence serum concentrations of insulin, cortisol, IGF-1, thyroxine, LH, or GH. Collectively, these observations contrast with the potent hypophagic effects of leptin when delivered intracerebroventricularly into well-fed lambs. The reasons for the disparate response of lambs treated intravenously with leptin, versus that reported for lambs treated intracerebroventricularly with leptin are not known, but may provide insight into the mechanism(s) of leptin resistance.
在绵羊中，瘦素的血清浓度会随着营养状况的增减而相应变化，而向脑室内注射瘦素会显著抑制饱食羔羊的采食量，并且可能还会增加营养不良羔羊的生长激素（GH）和/或促黄体生成素（LH）。本研究的目的是通过静脉输注来确定外周给予绵羊瘦素对采食量以及GH、LH、胰岛素、胰岛素样生长因子-1（IGF-1）、皮质醇和甲状腺素血清浓度的影响。将12只体重为29.4±0.7千克的母羊羔羊静脉输注线性递增剂量的瘦素或生理盐水（每组n = 6只），持续10天，在第10天达到最大输注剂量0.5毫克/小时。每天评估两次采食量，并在第0、2、5、8和10天每10分钟采集一次血样，共采集6小时。到第2天，接受瘦素治疗的羔羊血清瘦素浓度升高（P = 0.05），并持续升高，到第10天浓度比输注生理盐水的羔羊高9倍（P < 0.001）。尽管血清瘦素大幅增加，但除了在第3.5天外，瘦素组和生理盐水组羔羊的采食量并无差异（P = 0.01）。此外，静脉输注瘦素对胰岛素、皮质醇、IGF-1、甲状腺素、LH或GH的血清浓度没有显著影响。总体而言，这些观察结果与向饱食羔羊脑室内注射瘦素时其强大的促食欲减退作用形成对比。静脉注射瘦素的羔羊与脑室内注射瘦素的羔羊反应不同的原因尚不清楚，但可能有助于深入了解瘦素抵抗的机制。
