Blood-Brain Barrier Group, Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA 70808, USA.
J Appl Physiol (1985). 2012 Apr;112(8):1410-8. doi: 10.1152/japplphysiol.00590.2011. Epub 2012 Feb 9.
Leptin, a polypeptide hormone produced mainly by adipocytes, has diverse effects in both the brain and peripheral organs, including suppression of feeding. Other than mediating leptin transport across the blood-brain barrier, the role of the endothelial leptin receptor remains unclear. We recently generated a mutant mouse strain lacking endothelial leptin receptor signaling, and showed that there is an increased uptake of leptin by brain parenchyma after its delivery by in situ brain perfusion. Here, we tested the hypothesis that endothelial leptin receptor mutation confers partial resistance to diet-induced obesity. These ELKO mice had similar body weight and percent fat as their wild-type littermates when fed with rodent chow, but blood concentrations of leptin were significantly elevated. In response to a high-fat diet, wild-type mice had a greater gain of body weight and fat than ELKO mice. As shown by metabolic chamber measurement, the ELKO mice had higher oxygen consumption, carbon dioxide production, and heat dissipation, although food intake was similar to that of the wild-type mice and locomotor activity was even reduced. This indicates that the partial resistance to diet-induced obesity was mediated by higher metabolic activity in the ELKO mice. Since neuronal leptin receptor knockout mice show obesity and diabetes, the results suggest that endothelial leptin signaling shows opposite effects from that of neuronal leptin signaling, with a facilitatory role in diet-induced obesity.
瘦素是一种主要由脂肪细胞产生的多肽激素，在大脑和外周器官中具有多种作用，包括抑制进食。除了介导瘦素穿过血脑屏障的转运外，内皮瘦素受体的作用仍不清楚。我们最近生成了一种缺乏内皮瘦素受体信号的突变小鼠品系，并表明在原位脑灌注后，脑实质对瘦素的摄取增加。在这里，我们检验了内皮瘦素受体突变赋予部分抵抗饮食诱导肥胖的假设。当用啮齿动物饲料喂养时，这些 ELKO 小鼠的体重和体脂百分比与野生型同窝仔相似，但血液中的瘦素浓度明显升高。对高脂肪饮食的反应，野生型小鼠的体重和脂肪增加比 ELKO 小鼠更多。如代谢室测量所示，尽管 ELKO 小鼠的食物摄入量与野生型小鼠相似，且运动活性甚至降低，但 ELKO 小鼠的耗氧量、二氧化碳产生量和散热更高。这表明对饮食诱导肥胖的部分抵抗是由 ELKO 小鼠更高的代谢活性介导的。由于神经元瘦素受体敲除小鼠表现出肥胖和糖尿病，结果表明内皮瘦素信号与神经元瘦素信号具有相反的作用，在饮食诱导肥胖中起促进作用。
