Takekoshi K, Motooka M, Isobe K, Nomura F, Manmoku T, Ishii K, Nakai T
Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Tsukuba, 305-8575, Japan.
Biochem Biophys Res Commun. 1999 Aug 2;261(2):426-31. doi: 10.1006/bbrc.1999.1025.
Leptin, a protein encoded by the ob gene, is an adipose tissue-derived signaling factor involved in body weight homeostasis. The hypothalamus is a major site of central action for leptin. However, mounting evidence indicates expression of leptin receptor mRNA in various peripheral organs including the adrenal medulla. Therefore, we investigated the effects of leptin on catecholamine secretion and synthesis in cultured porcine adrenal medullary chromaffin cells. We initially confirmed the expression of leptin receptor (Ob-Rb) mRNA in cultured porcine adrenal medullary cells. Murine recombinant leptin (>==50 nM) strongly induced the release of both epinephrine (E) and norepinephrine (NE) from chromaffin cells. Removal of external Ca(2+) significantly suppressed these effects. Also, leptin (>==1 nM) enhanced nicotine-induced increases in E- and NE. Leptin (1, 10, 100 nM) significantly increased tyrosine hydroxylase (TH) (a rate-limiting enzyme in the biosynthesis of catecholamine) mRNA levels in a concentration-dependent manner. Furthermore, leptin (1, 10, 100 nM) significantly induced increases in cAMP levels, suggesting that the stimulatory effects on TH mRNA are mediated, at least in part, by the cAMP/protein kinase A pathway. These results indicate that leptin directly stimulates catecholamine release and synthesis, which in turn may potentiate the anti-obesity effects of leptin.
瘦素是一种由ob基因编码的蛋白质，是一种参与体重稳态调节的脂肪组织衍生信号因子。下丘脑是瘦素发挥中枢作用的主要部位。然而，越来越多的证据表明瘦素受体mRNA在包括肾上腺髓质在内的各种外周器官中均有表达。因此，我们研究了瘦素对培养的猪肾上腺髓质嗜铬细胞儿茶酚胺分泌和合成的影响。我们首先证实了瘦素受体（Ob-Rb）mRNA在培养的猪肾上腺髓质细胞中的表达。小鼠重组瘦素（≥50 nM）强烈诱导嗜铬细胞释放肾上腺素（E）和去甲肾上腺素（NE）。去除细胞外Ca(2+)可显著抑制这些作用。此外，瘦素（≥1 nM）增强了尼古丁诱导的E和NE的增加。瘦素（1、10、100 nM）以浓度依赖的方式显著增加酪氨酸羟化酶（TH）（儿茶酚胺生物合成中的限速酶）的mRNA水平。此外，瘦素（1、10、100 nM）显著诱导cAMP水平升高，表明对TH mRNA的刺激作用至少部分是由cAMP/蛋白激酶A途径介导的。这些结果表明，瘦素直接刺激儿茶酚胺的释放和合成，这反过来可能增强瘦素的抗肥胖作用。
