Department of Physiology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia.
Department of Physiology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia
Am J Physiol Endocrinol Metab. 2015 Mar 1;308(5):E351-61. doi: 10.1152/ajpendo.00501.2014. Epub 2014 Dec 30.
Leptin receptors (ObRs) in the forebrain and hindbrain have been independently recognized as important mediators of leptin responses. We recently used low-dose leptin infusions to show that chronic activation of both hypothalamic and hindbrain ObRs is required to reduce body fat. The objective of the present study was to identify the brain nuclei that are selectively activated in rats that received chronic infusion of leptin in both the forebrain and hindbrain. Either saline or leptin was infused into third and fourth ventricles (0.1 μg/24 h in the third ventricle and 0.6 μg/24 h in the fourth ventricle) of male Sprague-Dawley rats for 6 days using Alzet pumps. Rats infused with leptin into both ventricles (LL rats) showed a significant increase in phosphorylated (p)STAT3 immunoreactivity in the arcuate nucleus, ventromedial hypothalamus, dorsomedial hypothalamus, and posterior hypothalamus compared with other groups. No differences in pSTAT3 immunoreactivity were observed in midbrain or hindbrain nuclei despite a sixfold higher infusion of leptin into the fourth ventricle than the third ventricle. ΔFosB immunoreactivity, a marker of chronic neuronal activation, showed that multiple brain nuclei were chronically activated due to the process of infusion, but only the arcuate nucleus, ventromedial hypothalamus, dorsomedial hypothalamus, and ventral tuberomamillary nucleus showed a significant increase in LL rats compared with other groups. These data demonstrate that low-dose leptin in the hindbrain increases pSTAT3 in areas of the hypothalamus known to respond to leptin, supporting the hypothesis that leptin-induced weight loss requires an integrated response from both the hindbrain and forebrain.
瘦素受体（ObRs）在前脑和后脑中被独立认为是瘦素反应的重要介质。我们最近使用低剂量瘦素输注表明，慢性激活下丘脑和后脑 ObRs 是减少体脂肪所必需的。本研究的目的是确定在接受前脑和后脑中慢性输注瘦素的大鼠中，哪些脑核被选择性激活。使用 Alzet 泵，雄性 Sprague-Dawley 大鼠的第三和第四脑室（第三脑室中 0.1 μg/24 h，第四脑室中 0.6 μg/24 h）分别输注盐水或瘦素 6 天。与其他组相比，脑室中输注瘦素的大鼠（LL 大鼠）在弓状核、腹内侧下丘脑、背内侧下丘脑和后下丘脑的磷酸化（p）STAT3 免疫反应性显著增加。尽管第四脑室中的瘦素输注量是第三脑室的六倍，但中脑或后脑核中的 pSTAT3 免疫反应性没有差异。ΔFosB 免疫反应性是慢性神经元激活的标志物，表明由于输注过程，多个脑核被慢性激活，但只有弓状核、腹内侧下丘脑、背内侧下丘脑和腹侧结节乳头核在 LL 大鼠中与其他组相比显著增加。这些数据表明，后脑中的低剂量瘦素增加了已知对瘦素有反应的下丘脑区域的 pSTAT3，支持瘦素诱导的体重减轻需要后脑和前脑的综合反应的假设。
