Horwitz B A, Hamilton J S, Routh V H, Green K, Havel P, Chan A
Section of Neurobiology, Physiology, and Behavior, University of California, Davis, California 95616, USA.
Am J Physiol. 1998 Jun;274(6):E1009-17. doi: 10.1152/ajpendo.1998.274.6.E1009.
Decreased ventromedial hypothalamic (VMH) serotonergic activity occurs in genetic and diet-induced animal models of obesity. We previously found that this activity was lower in adult and in 12-day-old Zucker fa/fa vs. Fa/Fa pups, the fa/fa animals being identified by their greater adiposity. In the present study, we evaluated fa/fa rats (Brown Norway-Zucker hybrids) at ages 2, 4, 7, and 12 days to test the hypothesis that lower VMH serotonergic activity occurs before increased adiposity and/or attenuated energy expenditure. Our results negate this hypothesis. VMH serotonergic activity showed no consistent genotype differences even at 12 days of age. In contrast, by day 7, fa/fa vs. Fa/Fa pups had higher serum leptin concentrations, greater percent body fat, lower resting and cold-induced energy expenditure, and lower activity of brown fat thyroxine 5'-deiodinase, an enzyme that converts thyroxine to triiodothyronine. We conclude that the onset of increased adiposity induced by the fa gene does not require decreased VMH serotonergic activity and that the lower serotonergic activity seen in older fa/fa pups may be secondary to metabolic consequences of the disruption of the leptin regulatory pathway.
在遗传性和饮食诱导性肥胖动物模型中，腹内侧下丘脑（VMH）的血清素能活性降低。我们之前发现，成年和12日龄的Zucker fa/fa幼崽与Fa/Fa幼崽相比，这种活性较低，fa/fa动物的特征是更肥胖。在本研究中，我们评估了2日龄、4日龄、7日龄和12日龄的fa/fa大鼠（棕色挪威- Zucker杂交种），以检验VMH血清素能活性降低发生在肥胖增加和/或能量消耗减弱之前的假设。我们的结果否定了这一假设。即使在12日龄时，VMH血清素能活性也没有一致的基因型差异。相比之下，到7日龄时，fa/fa幼崽与Fa/Fa幼崽相比，血清瘦素浓度更高、体脂百分比更高、静息和冷诱导的能量消耗更低，以及棕色脂肪甲状腺素5'-脱碘酶（一种将甲状腺素转化为三碘甲状腺原氨酸的酶）的活性更低。我们得出结论，fa基因诱导的肥胖增加的起始并不需要VMH血清素能活性降低，并且在较大的fa/fa幼崽中看到的较低血清素能活性可能是瘦素调节途径破坏的代谢后果的继发表现。
