Effects of chronic central leptin infusion on proopiomelanocortin and neurotensin gene expression in the rat hypothalamus.
Effects of chronic central leptin infusion on proopiomelanocortin and neurotensin gene expression in the rat hypothalamus.
复制标题
慢性中枢瘦素输注对大鼠下丘脑阿黑皮质素原和神经降压素基因表达的影响。
DOI：
10.1016/j.neulet.2008.05.083
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发表时间：
2008
影响因子：
2.5
通讯作者：
Sahu,Abhiram
中科院分区：
文献类型：
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作者：
Sahu,Abhiram
下丘脑中的瘦素信号对正常的食物摄取和体重调节至关重要。虽然肥胖者的高瘦素血症表明瘦素抵抗的状态，但其机制尚不清楚。在中枢注射瘦素的大鼠模型中，动物对瘦素的饱腹感作用产生抵抗，下丘脑中产生食欲肽的神经肽Y神经元产生瘦素抵抗。然而，目前尚不清楚中枢注射瘦素引起的下丘脑瘦素张力增加是否会导致产生阿片黑素皮质素原(POMC)和神经降压素(NT)的厌氧肽神经元产生瘦素抵抗。为此，雄性大鼠将瘦素(160 ng/h)或赋形剂长期注入侧脑室16天。在注射瘦素的第4天，当摄食量减少时，核糖核酸酶保护试验测定的POMC和NT的mRNA水平显著高于对照组。相反，在注射瘦素的第16天，当食物摄入量基本正常时，POMC和NT的mRNA水平与对照组相比没有变化。这些发现提示，下丘脑瘦素张力慢性升高后，POMC和NT神经元出现了瘦素抵抗，这可能与中枢注射瘦素后对瘦素的饱足作用产生抵抗有关。
Leptin signaling in the hypothalamus is critical for normal food intake and body weight regulation. While hyperleptinemia in obese people suggests a state of leptin resistance, the mechanism is not clearly understood. In a rat model of central leptin infusion in which animals develop resistance to the satiety action of leptin, orexigenic peptide producing neuropeptide Y neurons in the hypothalamus develop leptin resistance. However, it is still unknown if increased hypothalamic leptin tone caused by central leptin infusion results in the development of leptin resistance in anorexigenic peptide producing proopiomelanocortin (POMC) and neurotensin (NT) neurons. To this end, male rats were infused chronically with leptin (160ng/h) or vehicle into the lateral cerebroventricle for 16 days. On day 4 of leptin infusion when food intake was decreased, POMC and NT mRNA levels, as determined by RNAse protection assay, were significantly increased as compared to control. By contrast, on day 16 of leptin infusion, when food intake was mostly normalized, both POMC and NT mRNA levels remained unchanged compared with control. These findings suggest the development of leptin resistance in the POMC and NT neurons following chronic elevation of hypothalamic leptin tone, which may be involved in the development of resistance to the satiety action of leptin following central infusion of this peptide hormone.